A Brief Clinical Overview of Retinitis Pigmentosa: History
View Latest Version
Please note this is an old version of this entry, which may differ significantly from the current revision.
Subjects: Ophthalmology
Contributor:
Kevin Yang Wu
,
An Qi Xu
,
Ananda Kalevar
,
Jasmeet Dhaliwal
,
Asif Jamal
,
Shrieda Jain
,
Simon D. Tran

Retinitis pigmentosa (RP) is a hereditary disease that causes the degeneration of photoreceptor cells in the retina, starting with the rods, leading to a gradual loss of vision over time. RP is the most common type of inherited retinal dystrophy and affects over 1.5 million people worldwide, leading to a high burden on patients and society [1]. Common symptoms of RP include nyctalopia and gradual loss of peripheral vision, which can ultimately lead to blindness. RP is one of the primary causes of visual disability and blindness in individuals under 60 years old.

  • retinitis pigmentosa
  • ER stress
  • retinal degeneration
  • photoreceptor cell death
  • therapeutictarget
  • neuroprotection
  • optogenetics
  • gene therapy
  • stem cell therapy
  • preclinical studies

Overview of Retinitis Pigmentosa

Classification

Retinitis pigmentosa (RP) can be classified into two categories: syndromic and non-syndromic.

Non-syndromic RP affects only the retina, with a prevalence of 1:5000 and can be caused by sporadic mutations or genetic predisposition [3]. The mode of inheritance is classified as autosomal dominant, autosomal recessive, or X-linked [4]. Genetic testing and family history are essential tools in determining the inheritance pattern and risk for RP.

Syndromic RP refers to a group of retinitis pigmentosa conditions, including Leber Congenital Amaurosis (LCA), Usher syndrome, and Bardet-Biedl syndrome. LCA is mainly inherited in an autosomal recessive pattern and is caused by mutations in the RPE65 gene. It is characterized by early vision loss, abnormal pupillary response, and nystagmus, typically appearing in infancy. Usher syndrome is the most common syndromic form of RP, affecting about 3 in every 100,000 people. It presents with typical RP symptoms, accompanied by varying levels of hearing and vestibular dysfunction depending on the subtype [5]. Bardet-Biedl syndrome is the second most frequent syndromic form of RP, with a prevalence of 1 in every 160,000 Northern Europeans [6]. It is caused by mutations in the BBS1-BBS21 genes, with BBS1 being the most common. This autosomal recessive disease is characterized by multisystemic symptoms, including polydactyly, genital abnormality, cognitive impairment, and classic RP symptoms that usually appear in the first decade of life.

Only two types of syndromic RP have clinically significant treatments to preserve vision, despite several rare forms being present [7]. Bassen-Kornzweig syndrome is an autosomal recessive disorder characterized by retinal and neurological degeneration due to deficiencies of vitamins A and E [8]. Vitamin A (300 IU/kg/day) and vitamin E (100 IU/kg/day) supplementation has been shown to slow retinal degeneration if started early [9]. Refsum disease, on the other hand, can be managed through weight control and restriction of phytanic acid-containing foods, as the accumulation of this acid is the primary cause of retinal and neurological degeneration due to a defective enzyme [9].

 

Signs and symptoms

The diagnostic of Retinitis Pigmentosa (RP) is based on clinical manifestations such as nyctalopia, peripheral visual field loss, and characteristic fundus changes. The diagnosis of RP is confirmed through abnormal electroretinogram (ERG) results. The typical fundus changes in RP include bone spicules hyperpigmentation and hypopigmentation, waxy disc pallor, and arteriolar narrowing. Additionally, there are two atypical fundus phenotypes, which are retinitis punctata albescens and choroideremia [2].

 

Management and Prognosis

RP's prognosis is challenging to establish due to the heterogeneity of gene mutations, leading to varied disease progression. Symptoms may onset in childhood or adulthood, and visual field loss progresses annually by 4-12% [10]. Autosomal dominant RP typically results in the least severe vision loss, whereas X-linked RP has the most severe manifestations and the worst prognosis [1]. The progression of visual field loss in RP generally begins with sectorial scotoma in the mid-peripheral areas, advancing to partial ring scotoma, complete ring scotoma, and ultimately culminating in total blindness. Standard medical follow-up for RP patients includes annual ophthalmic examination, which measures visual acuity and Goldmann visual field, dilated fundoscopy, optical coherence tomography (OCT), and occasionally fluorescein angiography (FA). Although ERG's a and b wave amplitude decline is a sensitive tool for assessing RP progression, it is not always necessary for annual follow-up [2].

Most RP patients will not become completely blind, as they retain some macular function even in their fourth decade of life [2]. In the panretinal dystrophy stage, RP patients commonly exhibit optic nerve head drusen, cystoid macular edema, vitreous cells, epiretinal membranes, and posterior subcapsular cataracts. Diminished visual acuity is often caused by the complications of cystoid macular edema and posterior capsular opacification.

Most patients with RP have no curative treatment available. Only patients with RPE65 gene mutation are eligible to receive target gene therapy. Conventional treatment options, such as vitamin A supplements, protection from sunlight, visual aids, and medical and surgical interventions, aim to manage symptoms, prevent ophthalmic complications, and slow the progression of the disease. However, these interventions do not provide a cure for the disease.

 

Conventional Treatments and Limitations

Dietary Supplements (Vitamin A, DHA, Lutein) [11]

Vitamin A is a fat-soluble vitamin that plays an important role in visual cycle, retinal pigment epithelium cell metabolism, and phototransduction [12]. Multiple randomized clinical trials on RP patients investigated the efficacy of vitamin A, DHA, and lutein as treatments. Vitamin A alone may slow the decline of ERG amplitude but did not significantly improve visual field area or visual acuity [13]. DHA did not show significant benefits when combined with vitamin A, but a subgroup analysis showed a slower visual field decline [14]. Lutein combined with vitamin A only resulted in a slower rate of decline in the total point score for the HFA 60-4 program [15]. Despite mixed results, the combination of vitamin A, lutein, and fish oil containing DHA is still recommended as therapy for RP patients. However, a systematic review concluded that there is no significant evidence to support the use of vitamin A, DHA, or a combination thereof for RP patients [12]. Regular use of high doses of Vitamin A can cause various side effects and complications [16]. Vitamin A treatment remains controversial due to its potential risks, but there is evidence supporting its effectiveness for a small, genetically distinct subgroup of RP patients with PRPH2-associated retinitis pigmentosa [17].

 

Cystoid Macular Edema (CME) Treatment

Cystoid macular edema (CME) is a common complication in RP cases, affecting up to 38% of patients and causing decreased visual acuity [18,19]. First-line treatments for CME include oral and topical carbonic anhydrase inhibitors, such as acetazolamide, methazolamide, dorzolamide, and brinzolamide, which have demonstrated significant benefits in multiple studies. Second-line treatments, such as intravitreal steroids injection, oral corticosteroids, anti-VEGF injection, and topical or local non-steroidal anti-inflammatory drugs (NSAIDs), have also proven to be effective pharmaceutical therapies for patients who do not respond to carbonic anhydrase inhibitors [20].

 

Protection from Sunlight

Due to its high metabolic rate and oxygen consumption, as well as the presence of photosensitizer molecules in the photoreceptors that are constantly exposed to light and oxidative stress, the retina is vulnerable to oxidative stress, leading to the accumulation of reactive oxygen species (ROS) in the retinal pigment epithelium (RPE). This can perpetuate a cycle of neuroinflammation and degeneration in RP, as demonstrated by multiple pathways [21]. Animal models of RP have shown that absence of light exposure was associated with a reduction in the rate of photoreceptor degeneration, while increased housing light intensity for rd10 mice accelerated retinal degeneration by activating cell death, oxidative stress pathways, and inflammatory cells [22]. Therefore, light protection may be a potential intervention to slow down the progression of the disease in some cases of RP [23]. However, there is a lack of convincing studies to confirm the hypothesis on whether sunlight deprivation slows down retinal degeneration in RP, as demonstrated by one case report of an RP patient with mono-ocular occlusion for over 40 years who had an equivalent fundus in both eyes.

 

Auxiliary Support

External Device

Visual aids can improve the quality of life of RP patients, such as night vision pocketscopes, goggles, or light-amplifying devices that can alleviate night blindness [24-26]. In a study by Ikeda et al. (2015), a research device designed to assist patients with RP-induced night blindness was found to be effective. The device was equipped with a camera that provided a minimum illuminance of 0.08 lux, and the subjects using the device achieved significantly higher success rates in completing a walking task in dimly lit rooms [27].

 

Surgicaly Implanted Device

ARGUS II prosthesis is an option for end-stage RP patients with bare light perception, but implantation of an epiretinal device is an invasive surgery, and only limited RP patients are candidates [28]. While participants in a phase II clinical trial of the ARGUS II had significantly better scores in all visual function tests, more than one-third of them experienced serious adverse events related to the device or surgery. Furthermore, the device is only beneficial for end-stage RP patients in allowing them to restore minimal vision, and RP patients with mild visual impairment would not benefit from it to restore normal vision [29]. Nonetheless, a recent study found that the safety profile of the Argus II has significantly improved compared to the pre-approval phase, with no significant issues reported up to four years post-implantation [30].

Overall, the conventional treatments listed above have limitations, and most of them do not target the underlying pathogenesis of RP.

 

Recent Therapeutic Advances

Gene therapy is a promising approach for treating RP, targeting the genetic causes of the condition.

Currently, Luxturna is the only approved gene therapy for RP, authorized only for a small sub-population of RP patients with the RPE65 gene mutation. This mutation is responsible for vitamin A metabolism and Leber congenital amaurosis (LCA). A phase III clinical trial demonstrated significant visual function improvement and no serious adverse events after one year with voretigene neparvovec, an adeno-associated virus (AAV2) vector containing modified human RPE65, and durability of improvement after three to four years of follow-up [31-33]. This success has led to ongoing clinical trials targeting other gene mutations associated with RP.

In the following sections, we will discuss novel therapeutic targets in the preclinical phase, including gene therapy, cell therapy, optogenetics, neuroprotective agents, exosome therapy, and novel treatment targets identified in recent literature.

 

[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64][65][66][67][68][69][70][71][72][73][74][75][76][77][78][79][80][81][82][83][84][85][86][87][88][89][90][91][92][93][94][95][96][97][98][99][100][101][102][103][104][105][106][107][108][109][110][111][112][113][114][115][116][117][118][119][120][121][122][123][124][125][126][127][128][129][130][131][132][133][134][135][136][137][138][139][140][141][142][143][144][145][146][147][148][149][150][151][152][153][154][155][156][157][158][159][160][161][162][163][164][165][166][167][168][169][170][171][172][173][174][175][176][177][178][179][180][181][182][183][184][185][186][187][188][189][190][191][192][193][194][195][196][197][198][199][200][201][202][203][204][205][206][207][208][209][210][211][212][213][214][215][216][217][218][219][220][221][222][223][224][225][226][227][228][229][230][231][232][233][234][235][236][237][238][239][240]

This entry is adapted from the peer-reviewed paper 10.3390/pharmaceutics15020685

References

  1. Cross, N.; van Steen, C.; Zegaoui, Y.; Satherley, A.; Angelillo, L. Retinitis Pigmentosa: Burden of Disease and Current Unmet Needs. Clin. Ophthalmol. 2022, 16, 1993–2010. [Google Scholar] [CrossRef]
  2. Retinitis Pigmentosa: Study Guide. Available online: https://www.aao.org/Assets/bcc226cb-7ac7-443c-897e-9b20afdfacfb/637153836910470000/r38u-pdf?inline=1&fbclid=IwAR2oP_lD1pWSAROpIfa9poqhZzeSf29_PvZztBZMSQfWKNqTbv1b6t0BXJU (accessed on 15 December 2022).
  3. O’Neal, T.B.; Luther, E.E. Retinitis Pigmentosa. In StatPearls; StatPearls Publishing: Treasure Island, FL, USA, 2022. [Google Scholar]
  4. Hartong, D.T.; Berson, E.L.; Dryja, T.P. Retinitis Pigmentosa. Lancet 2006, 368, 1795–1809. [Google Scholar] [CrossRef] [PubMed]
  5. Kimberling, W.J.; Hildebrand, M.S.; Shearer, A.E.; Jensen, M.L.; Halder, J.A.; Trzupek, K.; Cohn, E.S.; Weleber, R.G.; Stone, E.M.; Smith, R.J.H. Frequency of Usher Syndrome in Two Pediatric Populations: Implications for Genetic Screening of Deaf and Hard of Hearing Children. Genet. Med. Off. J. Am. Coll. Med. Genet. 2010, 12, 512–516. [Google Scholar] [CrossRef] [PubMed][Green Version]
  6. Weihbrecht, K. Bardet-Biedl Syndrome. In Genetics and Genomics of Eye Disease; Elsevier: Amsterdam, The Netherlands, 2020; pp. 117–136. ISBN 978-0-12-816222-4. [Google Scholar]
  7. Von Sallmann, L.; Gelderman, A.H.; Laster, L. Ocular Histopathologic Changes in a Case of A-Beta-Lipoproteinemia (Bassen-Kornzweig Syndrome). Doc. Ophthalmol. Adv. Ophthalmol. 1969, 26, 451–460. [Google Scholar] [CrossRef] [PubMed]
  8. Grant, C.A.; Berson, E.L. Treatable Forms of Retinitis Pigmentosa Associated with Systemic Neurological Disorders. Int. Ophthalmol. Clin. 2001, 41, 103–110. [Google Scholar] [CrossRef]
  9. Gibberd, F.B.; Billimoria, J.D.; Goldman, J.M.; Clemens, M.E.; Evans, R.; Whitelaw, M.N.; Retsas, S.; Sherratt, R.M. Heredopathia Atactica Polyneuritiformis: Refsum’s Disease. Acta Neurol. Scand. 1985, 72, 1–17. [Google Scholar] [CrossRef]
  10. Berson, E.L.; Sandberg, M.A.; Rosner, B.; Birch, D.G.; Hanson, A.H. Natural Course of Retinitis Pigmentosa over a Three-Year Interval. Am. J. Ophthalmol. 1985, 99, 240–251. [Google Scholar] [CrossRef]
  11. Wang, A.L.; Knight, D.K.; Vu, T.-T.T.; Mehta, M.C. Retinitis Pigmentosa: Review of Current Treatment. Int. Ophthalmol. Clin. 2019, 59, 263–280. [Google Scholar] [CrossRef]
  12. Rayapudi, S.; Schwartz, S.G.; Wang, X.; Chavis, P. Vitamin A and Fish Oils for Retinitis Pigmentosa. Cochrane Libr. Cochrane Rev. 2013, 2013, CD008428. [Google Scholar] [CrossRef][Green Version]
  13. Berson, E.L. Retinitis Pigmentosa. The Friedenwald Lecture. Investig. Ophthalmol. Vis. Sci. 1993, 34, 1659–1676. [Google Scholar]
  14. Berson, E.L.; Rosner, B.; Sandberg, M.A.; Weigel-DiFranco, C.; Moser, A.; Brockhurst, R.J.; Hayes, K.C.; Johnson, C.A.; Anderson, E.J.; Gaudio, A.R.; et al. Further Evaluation of Docosahexaenoic Acid in Patients with Retinitis Pigmentosa Receiving Vitamin A Treatment: Subgroup Analyses. Arch. Ophthalmol. 2004, 122, 1306–1314. [Google Scholar] [CrossRef] [PubMed]
  15. Berson, E.L.; Rosner, B.; Sandberg, M.A.; Weigel-DiFranco, C.; Brockhurst, R.J.; Hayes, K.C.; Johnson, E.J.; Anderson, E.J.; Johnson, C.A.; Gaudio, A.R.; et al. Clinical Trial of Lutein in Patients with Retinitis Pigmentosa Receiving Vitamin A. Arch. Ophthalmol. 2010, 128, 403–411. [Google Scholar] [CrossRef] [PubMed][Green Version]
  16. Russell, R.M. The Vitamin A Spectrum: From Deficiency to Toxicity. Am. J. Clin. Nutr. 2000, 71, 878–884. [Google Scholar] [CrossRef] [PubMed][Green Version]
  17. Pierce, E.A.; Bujakowska, K.M.; Place, E.; Navarro-Gomez, D.; Maher, M.; Weigel-DFranco, C.; Comander, J. The Effect Of Vitamin A On Progression Of Retinitis Pigmentosa Is Not Determined By The Underlying Genetic Cause Of Disease. Investig. Ophthalmol. Vis. Sci. 2017, 58, 2011. [Google Scholar]
  18. Hajali, M.; Fishman, G.A.; Anderson, R.J. The Prevalence of Cystoid Macular Oedema in Retinitis Pigmentosa Patients Determined by Optical Coherence Tomography. Br. J. Ophthalmol. 2008, 92, 1065–1068. [Google Scholar] [CrossRef] [PubMed]
  19. Ozdemir, H.; Karacorlu, M.; Karacorlu, S. Intravitreal Triamcinolone Acetonide for Treatment of Cystoid Macular Oedema in Patients with Retinitis Pigmentosa. Acta Ophthalmol. Scand. 2005, 83, 248–251. [Google Scholar] [CrossRef]
  20. Bakthavatchalam, M.; Lai, F.H.P.; Rong, S.S.; Ng, D.S.; Brelen, M.E. Treatment of Cystoid Macular Edema Secondary to Retinitis Pigmentosa: A Systematic Review. Surv. Ophthalmol. 2018, 63, 329–339. [Google Scholar] [CrossRef]
  21. Gallenga, C.E.; Lonardi, M.; Pacetti, S.; Violanti, S.S.; Tassinari, P.; Di Virgilio, F.; Tognon, M.; Perri, P. Molecular Mechanisms Related to Oxidative Stress in Retinitis Pigmentosa. Antioxidants 2021, 10, 848. [Google Scholar] [CrossRef]
  22. Naash, M.L.; Peachey, N.S.; Li, Z.Y.; Gryczan, C.C.; Goto, Y.; Blanks, J.; Milam, A.H.; Ripps, H. Light-Induced Acceleration of Photoreceptor Degeneration in Transgenic Mice Expressing Mutant Rhodopsin. Investig. Ophthalmol. Vis. Sci. 1996, 37, 775–782. [Google Scholar]
  23. Kutsyr, O.; Sánchez-Sáez, X.; Martínez-Gil, N.; de Juan, E.; Lax, P.; Maneu, V.; Cuenca, N. Gradual Increase in Environmental Light Intensity Induces Oxidative Stress and Inflammation and Accelerates Retinal Neurodegeneration. Investig. Ophthalmol. Vis. Sci. 2020, 61, 1. [Google Scholar] [CrossRef]
  24. Berson, E.L.; Rabin, A.R.; Mehaffey, L. Advances in Night Vision Technology. A Pocketscope for Patients with Retinitis Pigmentosa. Arch. Ophthalmol. 1973, 90, 427–431. [Google Scholar] [CrossRef] [PubMed]
  25. Hartong, D.T.; Jorritsma, F.F.; Neve, J.J.; Melis-Dankers, B.J.M.; Kooijman, A.C. Improved Mobility and Independence of Night-Blind People Using Night-Vision Goggles. Investig. Ophthalmol. Vis. Sci. 2004, 45, 1725–1731. [Google Scholar] [CrossRef] [PubMed][Green Version]
  26. Mancil, R.M.; Mancil, G.L.; King, E.; Legault, C.; Munday, J.; Alfieri, S.; Nowakowski, R.; Blasch, B.B. Improving Nighttime Mobility in Persons with Night Blindness Caused by Retinitis Pigmentosa: A Comparison of Two Low-Vision Mobility Devices. J. Rehabil. Res. Dev. 2005, 42, 471–486. [Google Scholar] [CrossRef] [PubMed][Green Version]
  27. Ikeda, Y.; Suzuki, E.; Kuramata, T.; Kozaki, T.; Koyama, T.; Kato, Y.; Murakami, Y.; Enaida, H.; Ishibashi, T. Development and Evaluation of a Visual Aid Using See-through Display for Patients with Retinitis Pigmentosa. Jpn. J. Ophthalmol. 2015, 59, 43–47. [Google Scholar] [CrossRef]
  28. Humayun, M.S.; Dorn, J.D.; da Cruz, L.; Dagnelie, G.; Sahel, J.-A.; Stanga, P.E.; Cideciyan, A.V.; Duncan, J.L.; Eliott, D.; Filley, E.; et al. Interim Results from the International Trial of Second Sight’s Visual Prosthesis. Ophthalmology 2012, 119, 779–788. [Google Scholar] [CrossRef][Green Version]
  29. da Cruz, L.; Dorn, J.D.; Humayun, M.S.; Dagnelie, G.; Handa, J.; Barale, P.-O.; Sahel, J.-A.; Stanga, P.E.; Hafezi, F.; Safran, A.B.; et al. Five-Year Safety and Performance Results from the Argus II Retinal Prosthesis System Clinical Trial. Ophthalmology 2016, 123, 2248–2254. [Google Scholar] [CrossRef][Green Version]
  30. Arevalo, J.F.; Al Rashaed, S.; Alhamad, T.A.; Al Kahtani, E.; Al-Dhibi, H.A.; for the KKESH Collaborative Retina Study Group; Mura, M.; Al Kahtani, E.; Nowilaty, S.; Al Rashaed, S.; et al. Argus II Retinal Prosthesis for Retinitis Pigmentosa in the Middle East: The 2015 Pan-American Association of Ophthalmology Gradle Lecture. Int. J. Retin. Vitr. 2021, 7, 65. [Google Scholar] [CrossRef]
  31. Russell, S.; Bennett, J.; Wellman, J.A.; Chung, D.C.; Yu, Z.-F.; Tillman, A.; Wittes, J.; Pappas, J.; Elci, O.; McCague, S.; et al. Efficacy and Safety of Voretigene Neparvovec (AAV2-HRPE65v2) in Patients with RPE65-Mediated Inherited Retinal Dystrophy: A Randomised, Controlled, Open-Label, Phase 3 Trial. Lancet 2017, 390, 849–860. [Google Scholar] [CrossRef]
  32. Maguire, A.M.; Russell, S.; Wellman, J.A.; Chung, D.C.; Yu, Z.-F.; Tillman, A.; Wittes, J.; Pappas, J.; Elci, O.; Marshall, K.A.; et al. Efficacy, Safety, and Durability of Voretigene Neparvovec-Rzyl in RPE65 Mutation-Associated Inherited Retinal Dystrophy: Results of Phase 1 and 3 Trials. Ophthalmology 2019, 126, 1273–1285. [Google Scholar] [CrossRef][Green Version]
  33. Maguire, A.M.; Russell, S.; Chung, D.C.; Yu, Z.-F.; Tillman, A.; Drack, A.V.; Simonelli, F.; Leroy, B.P.; Reape, K.Z.; High, K.A.; et al. Durability of Voretigene Neparvovec for Biallelic RPE65-Mediated Inherited Retinal Disease: Phase 3 Results at 3 and 4 Years. Ophthalmology 2021, 128, 1460–1468. [Google Scholar] [CrossRef]
  34. Dhurandhar, D.; Sahoo, N.; Mariappan, I.; Narayanan, R. Gene Therapy in Retinal Diseases: A Review. Indian J. Ophthalmol. 2021, 69, 2257–2265. [Google Scholar] [CrossRef] [PubMed]
  35. Ong, T.; Pennesi, M.E.; Birch, D.G.; Lam, B.L.; Tsang, S.H. Adeno-Associated Viral Gene Therapy for Inherited Retinal Disease. Pharm. Res. 2019, 36, 34. [Google Scholar] [CrossRef] [PubMed]
  36. Bulcha, J.T.; Wang, Y.; Ma, H.; Tai, P.W.L.; Gao, G. Viral Vector Platforms within the Gene Therapy Landscape. Signal Transduct. Target. Ther. 2021, 6, 53. [Google Scholar] [CrossRef] [PubMed]
  37. Berns, K.I.; Giraud, C. Biology of Adeno-Associated Virus. In Adeno-Associated Virus (AAV) Vectors in Gene Therapy; Berns, K.I., Giraud, C., Eds.; Current Topics in Microbiology and Immunology; Springer: Berlin/Heidelberg, Germany, 1996; Volume 218, pp. 1–23. ISBN 978-3-642-80209-6. [Google Scholar]
  38. Trapani, I.; Puppo, A.; Auricchio, A. Vector Platforms for Gene Therapy of Inherited Retinopathies. Prog. Retin. Eye Res. 2014, 43, 108–128. [Google Scholar] [CrossRef][Green Version]
  39. Chen, H.; Xiang, Z.Q.; Li, Y.; Kurupati, R.K.; Jia, B.; Bian, A.; Zhou, D.M.; Hutnick, N.; Yuan, S.; Gray, C.; et al. Adenovirus-Based Vaccines: Comparison of Vectors from Three Species of Adenoviridae. J. Virol. 2010, 84, 10522–10532. [Google Scholar] [CrossRef][Green Version]
  40. Kotin, R.M.; Menninger, J.C.; Ward, D.C.; Berns, K.I. Mapping and Direct Visualization of a Region-Specific Viral DNA Integration Site on Chromosome 19q13-Qter. Genomics 1991, 10, 831–834. [Google Scholar] [CrossRef]
  41. Qu, Y.; Liu, Y.; Noor, A.; Tran, J.; Li, R. Characteristics and Advantages of Adeno-Associated Virus Vector-Mediated Gene Therapy for Neurodegenerative Diseases. Neural Regen. Res. 2019, 14, 931. [Google Scholar] [CrossRef]
  42. Trapani, I.; Tornabene, P.; Auricchio, A. Large Gene Delivery to the Retina with AAV Vectors: Are We There Yet? Gene Ther. 2021, 28, 220–222. [Google Scholar] [CrossRef] [PubMed]
  43. Patel, A.; Zhao, J.; Duan, D.; Lai, Y. Design of AAV Vectors for Delivery of Large or Multiple Transgenes. In Adeno-Associated Virus Vectors; Castle, M.J., Ed.; Methods in Molecular Biology; Springer: New York, NY, USA, 2019; Volume 1950, pp. 19–33. ISBN 978-1-4939-9138-9. [Google Scholar]
  44. Tornabene, P.; Trapani, I. Can Adeno-Associated Viral Vectors Deliver Effectively Large Genes? Hum. Gene Ther. 2020, 31, 47–56. [Google Scholar] [CrossRef]
  45. Carvalho, L.S.; Turunen, H.T.; Wassmer, S.J.; Luna-Velez, M.V.; Xiao, R.; Bennett, J.; Vandenberghe, L.H. Evaluating Efficiencies of Dual AAV Approaches for Retinal Targeting. Front. Neurosci. 2017, 11, 503. [Google Scholar] [CrossRef]
  46. Maddalena, A.; Tornabene, P.; Tiberi, P.; Minopoli, R.; Manfredi, A.; Mutarelli, M.; Rossi, S.; Simonelli, F.; Naggert, J.K.; Cacchiarelli, D.; et al. Triple Vectors Expand AAV Transfer Capacity in the Retina. Mol. Ther. 2018, 26, 524–541. [Google Scholar] [CrossRef] [PubMed][Green Version]
  47. McClements, M.E.; Barnard, A.R.; Singh, M.S.; Charbel Issa, P.; Jiang, Z.; Radu, R.A.; MacLaren, R.E. An AAV Dual Vector Strategy Ameliorates the Stargardt Phenotype in Adult Abca4−/− Mice. Hum. Gene Ther. 2019, 30, 590–600. [Google Scholar] [CrossRef] [PubMed]
  48. Pavlou, M.; Schön, C.; Occelli, L.M.; Rossi, A.; Meumann, N.; Boyd, R.F.; Bartoe, J.T.; Siedlecki, J.; Gerhardt, M.J.; Babutzka, S.; et al. Novel AAV Capsids for Intravitreal Gene Therapy of Photoreceptor Disorders. EMBO Mol. Med. 2021, 13, e13392. [Google Scholar] [CrossRef]
  49. Kevany, B.; Suh, S.; Lu, J.; Padegimas, L.; Palczewski, K.; Miller, T. Novel AAV Capsids Demonstrate Strong Retinal Expression in Non-Human Primates After Intravitreal Administration. Investig. Ophthalmol. Vis. Sci. 2019, 60, 2900. [Google Scholar]
  50. Katada, Y.; Kobayashi, K.; Tsubota, K.; Kurihara, T. Evaluation of AAV-DJ Vector for Retinal Gene Therapy. PeerJ 2019, 7, e6317. [Google Scholar] [CrossRef]
  51. Leonova, E.I.; Gainetdinov, R.R. CRISPR/Cas9 Technology in Translational Biomedicine|Cell Physiol Biochem. Cell. Physiol. Biochem. 2020, 54, 354–370. [Google Scholar]
  52. Doudna, J.A.; Charpentier, E. The New Frontier of Genome Engineering with CRISPR-Cas9. Science 2014, 346, 1258096. [Google Scholar] [CrossRef]
  53. Peddle, C.F.; MacLaren, R.E. The Application of CRISPR/Cas9 for the Treatment of Retinal Diseases. Yale J. Biol. Med. 2017, 90, 533–541. [Google Scholar]
  54. Ahmad, I. CRISPR/Cas9-A Promising Therapeutic Tool to Cure Blindness: Current Scenario and Future Prospects. Int. J. Mol. Sci. 2022, 23, 11482. [Google Scholar] [CrossRef]
  55. Reshetnikov, V.V.; Chirinskaite, A.V.; Sopova, J.V.; Ivanov, R.A.; Leonova, E.I. Cas-Based Systems for RNA Editing in Gene Therapy of Monogenic Diseases: In Vitro and in Vivo Application and Translational Potential. Front. Cell Dev. Biol. 2022, 10, 903812. [Google Scholar] [CrossRef]
  56. Hu, Y.; Chen, Y.; Xu, J.; Wang, X.; Luo, S.; Mao, B.; Zhou, Q.; Li, W. Metagenomic Discovery of Novel CRISPR-Cas13 Systems. Cell Discov. 2022, 8, 107. [Google Scholar] [CrossRef] [PubMed]
  57. Botto, C.; Dalkara, D.; El-Amraoui, A. Progress in Gene Editing Tools and Their Potential for Correcting Mutations Underlying Hearing and Vision Loss. Front. Genome Ed. 2021, 3, 737632. [Google Scholar] [CrossRef] [PubMed]
  58. Wang, Q.; Liu, X.; Zhou, J.; Yang, C.; Wang, G.; Tan, Y.; Wu, Y.; Zhang, S.; Yi, K.; Kang, C. The CRISPR-Cas13a Gene-Editing System Induces Collateral Cleavage of RNA in Glioma Cells. Adv. Sci. 2019, 6, 1901299. [Google Scholar] [CrossRef] [PubMed][Green Version]
  59. Li, Y.; Xu, J.; Guo, X.; Li, Z.; Cao, L.; Liu, S.; Guo, Y.; Wang, G.; Luo, Y.; Zhang, Z.; et al. The Collateral Activity of RfxCas13d Can Induce Lethality in a RfxCas13d Knock-in Mouse Model. Genome Biol. 2023, 24, 20. [Google Scholar] [CrossRef]
  60. Ai, Y.; Liang, D.; Wilusz, J.E. CRISPR/Cas13 Effectors Have Differing Extents of off-Target Effects That Limit Their Utility in Eukaryotic Cells. Nucleic Acids Res. 2022, 50, e65. [Google Scholar] [CrossRef]
  61. Wu, Q.-W.; Kapfhammer, J.P. The Bacterial Enzyme Cas13 Interferes with Neurite Outgrowth from Cultured Cortical Neurons. Toxins 2021, 13, 262. [Google Scholar] [CrossRef]
  62. Fry, L.E.; McClements, M.E.; MacLaren, R.E. Comparison of CRISPR-Cas13 RNA Editing Tools for Inherited Retinal Disease. Investig. Ophthalmol. Vis. Sci. 2022, 63, 3845. [Google Scholar]
  63. Gemayel, M.C.; Bhatwadekar, A.D.; Ciulla, T. RNA Therapeutics for Retinal Diseases. Expert Opin. Biol. Ther. 2021, 21, 603–613. [Google Scholar] [CrossRef]
  64. Hannon, G.J. RNA Interference. Nature 2002, 418, 244–251. [Google Scholar] [CrossRef]
  65. Orlans, H.O.; McClements, M.E.; Barnard, A.R.; Martinez-Fernandez de la Camara, C.; MacLaren, R.E. Mirtron-Mediated RNA Knockdown/Replacement Therapy for the Treatment of Dominant Retinitis Pigmentosa. Nat. Commun. 2021, 12, 4934. [Google Scholar] [CrossRef]
  66. Bajan, S.; Hutvagner, G. RNA-Based Therapeutics: From Antisense Oligonucleotides to MiRNAs. Cells 2020, 9, 137. [Google Scholar] [CrossRef] [PubMed][Green Version]
  67. Knott, S.R.V.; Maceli, A.; Erard, N.; Chang, K.; Marran, K.; Zhou, X.; Gordon, A.; Demerdash, O.E.; Wagenblast, E.; Kim, S.; et al. A Computational Algorithm to Predict ShRNA Potency. Mol. Cell 2014, 56, 796–807. [Google Scholar] [CrossRef] [PubMed][Green Version]
  68. Liu, W.; Liu, S.; Li, P.; Yao, K. Retinitis Pigmentosa: Progress in Molecular Pathology and Biotherapeutical Strategies. Int. J. Mol. Sci. 2022, 23, 4883. [Google Scholar] [CrossRef] [PubMed]
  69. Cross, N.; van Steen, C.; Zegaoui, Y.; Satherley, A.; Angelillo, L. Current and Future Treatment of Retinitis Pigmentosa. Clin. Ophthalmol. 2022, 16, 2909–2921. [Google Scholar] [CrossRef] [PubMed]
  70. Parain, K.; Lourdel, S.; Donval, A.; Chesneau, A.; Borday, C.; Bronchain, O.; Locker, M.; Perron, M. CRISPR/Cas9-Mediated Models of Retinitis Pigmentosa Reveal Differential Proliferative Response of Müller Cells between Xenopus Laevis and Xenopus Tropicalis. Cells 2022, 11, 807. [Google Scholar] [CrossRef]
  71. Rana, T.; Shinde, V.M.; Starr, C.R.; Kruglov, A.A.; Boitet, E.R.; Kotla, P.; Zolotukhin, S.; Gross, A.K.; Gorbatyuk, M.S. An Activated Unfolded Protein Response Promotes Retinal Degeneration and Triggers an Inflammatory Response in the Mouse Retina. Cell Death Dis. 2014, 5, e1578. [Google Scholar] [CrossRef][Green Version]
  72. Inoue, C.; Takeuchi, T.; Shiota, A.; Kondo, M.; Nshizawa, Y. A Rat Model for Retinitis Pigmentosa with Rapid Retinal Degeneration Enables Drug Evaluation in Vivo. Biol. Proced. Online 2021, 23, 11. [Google Scholar] [CrossRef]
  73. Marrocco, E.; Maritato, R.; Botta, S.; Esposito, M.; Surace, E.M. Challenging Safety and Efficacy of Retinal Gene Therapies by Retinogenesis. Int. J. Mol. Sci. 2021, 22, 5767. [Google Scholar] [CrossRef]
  74. Bakondi, B.; Lv, W.; Lu, B.; Jones, M.K.; Tsai, Y.; Kim, K.J.; Levy, R.; Akhtar, A.A.; Breunig, J.J.; Svendsen, C.N.; et al. In Vivo CRISPR/Cas9 Gene Editing Corrects Retinal Dystrophy in the S334ter-3 Rat Model of Autosomal Dominant Retinitis Pigmentosa. Mol. Ther. 2016, 24, 556–563. [Google Scholar] [CrossRef][Green Version]
  75. Karali, M.; Guadagnino, I.; Marrocco, E.; De Cegli, R.; Carissimo, A.; Pizzo, M.; Casarosa, S.; Conte, I.; Surace, E.M.; Banfi, S. AAV-MiR-204 Protects from Retinal Degeneration by Attenuation of Microglia Activation and Photoreceptor Cell Death. Mol. Ther.-Nucleic Acids 2020, 19, 144–156. [Google Scholar] [CrossRef]
  76. Cuevas, E.; Holder, D.L.; Alshehri, A.H.; Tréguier, J.; Lakowski, J.; Sowden, J.C. NRL−/− Gene Edited Human Embryonic Stem Cells Generate Rod-Deficient Retinal Organoids Enriched in S-Cone-like Photoreceptors. Stem Cells 2021, 39, 414–428. [Google Scholar] [CrossRef] [PubMed]
  77. Yu, W.; Mookherjee, S.; Chaitankar, V.; Hiriyanna, S.; Kim, J.-W.; Brooks, M.; Ataeijannati, Y.; Sun, X.; Dong, L.; Li, T.; et al. Nrl Knockdown by AAV-Delivered CRISPR/Cas9 Prevents Retinal Degeneration in Mice. Nat. Commun. 2017, 8, 14716. [Google Scholar] [CrossRef] [PubMed][Green Version]
  78. Zhu, J.; Ming, C.; Fu, X.; Duan, Y.; Hoang, D.A.; Rutgard, J.; Zhang, R.; Wang, W.; Hou, R.; Zhang, D.; et al. Gene and Mutation Independent Therapy via CRISPR-Cas9 Mediated Cellular Reprogramming in Rod Photoreceptors. Cell Res. 2017, 27, 830–833. [Google Scholar] [CrossRef] [PubMed][Green Version]
  79. Xi, Z.; Vats, A.; Sahel, J.-A.; Chen, Y.; Byrne, L.C. Gene Augmentation Prevents Retinal Degeneration in a CRISPR/Cas9-Based Mouse Model of PRPF31 Retinitis Pigmentosa. Nat. Commun. 2022, 13, 7695. [Google Scholar] [CrossRef] [PubMed]
  80. Collin, C.; Liu, Q. CRISPR/Cas9-Based Genome Editing Approaches for RP1 Associated Autosomal Dominant Retinitis Pigmentosa. Investig. Ophthalmol. Vis. Sci. 2021, 62, 1486. [Google Scholar]
  81. Roman-Sanchez, R.; Wensel, T.G.; Wilson, J.H. Nonsense Mutations in the Rhodopsin Gene That Give Rise to Mild Phenotypes Trigger MRNA Degradation in Human Cells by Nonsense-Mediated Decay. Exp. Eye Res. 2016, 145, 444–449. [Google Scholar] [CrossRef] [PubMed][Green Version]
  82. Gumerson, J.D.; Alsufyani, A.; Yu, W.; Lei, J.; Sun, X.; Dong, L.; Wu, Z.; Li, T. Restoration of RPGR Expression in Vivo Using CRISPR/Cas9 Gene Editing. Gene Ther. 2022, 29, 81–93. [Google Scholar] [CrossRef]
  83. Hu, S.; Du, J.; Chen, N.; Jia, R.; Zhang, J.; Liu, X.; Yang, L. In Vivo CRISPR/Cas9-Mediated Genome Editing Mitigates Photoreceptor Degeneration in a Mouse Model of X-Linked Retinitis Pigmentosa. Investig. Ophthalmol. Vis. Sci. 2020, 61, 31. [Google Scholar] [CrossRef][Green Version]
  84. Michalakis, S.; Koch, S.; Sothilingam, V.; Garrido, M.G.; Tanimoto, N.; Schulze, E.; Becirovic, E.; Koch, F.; Seide, C.; Beck, S.C.; et al. Gene Therapy Restores Vision and Delays Degeneration in the CNGB1−/− Mouse Model of Retinitis Pigmentosa. In Retinal Degenerative Diseases; Ash, J.D., Grimm, C., Hollyfield, J.G., Anderson, R.E., LaVail, M.M., Bowes Rickman, C., Eds.; Advances in Experimental Medicine and Biology; Springer: New York, NY, USA, 2014; Volume 801, pp. 733–739. ISBN 978-1-4614-3208-1. [Google Scholar]
  85. Jia, D.; Gao, P.; Lv, Y.; Huang, Y.; Reilly, J.; Sun, K.; Han, Y.; Hu, H.; Chen, X.; Zhang, Z.; et al. Tulp1 Deficiency Causes Early-Onset Retinal Degeneration through Affecting Ciliogenesis and Activating Ferroptosis in Zebrafish. Cell Death Dis. 2022, 13, 962. [Google Scholar] [CrossRef]
  86. Palfi, A.; Yesmambetov, A.; Millington-Ward, S.; Shortall, C.; Humphries, P.; Kenna, P.F.; Chadderton, N.; Farrar, G.J. AAV-Delivered Tulp1 Supplementation Therapy Targeting Photoreceptors Provides Minimal Benefit in Tulp1−/− Retinas. Front. Neurosci. 2020, 14, 891. [Google Scholar] [CrossRef]
  87. Beryozkin, A.; Matsevich, C.; Obolensky, A.; Kostic, C.; Arsenijevic, Y.; Wolfrum, U.; Banin, E.; Sharon, D. A New Mouse Model for Retinal Degeneration Due to Fam161a Deficiency. Sci. Rep. 2021, 11, 2030. [Google Scholar] [CrossRef] [PubMed]
  88. Matsevich, C.; Gopalakrishnan, P.; Obolensky, A.; Banin, E.; Sharon, D.; Beryozkin, A. Retinal Structure and Function in a Knock-in Mouse Model for the FAM161A-p.Arg523∗ Human Nonsense Pathogenic Variant. Ophthalmol. Sci. 2023, 3, 100229. [Google Scholar] [CrossRef] [PubMed]
  89. García Bohórquez, B.; Aller, E.; Rodríguez Muñoz, A.; Jaijo, T.; García García, G.; Millán, J.M. Updating the Genetic Landscape of Inherited Retinal Dystrophies. Front. Cell Dev. Biol. 2021, 9, 645600. [Google Scholar] [CrossRef] [PubMed]
  90. Nash, B.M.; Wright, D.C.; Grigg, J.R.; Bennetts, B.; Jamieson, R.V. Retinal Dystrophies, Genomic Applications in Diagnosis and Prospects for Therapy. Transl. Pediatr. 2015, 4, 139–163. [Google Scholar] [CrossRef]
  91. Perea-Romero, I.; Gordo, G.; Iancu, I.F.; Del Pozo-Valero, M.; Almoguera, B.; Blanco-Kelly, F.; Carreño, E.; Jimenez-Rolando, B.; Lopez-Rodriguez, R.; Lorda-Sanchez, I.; et al. Genetic Landscape of 6089 Inherited Retinal Dystrophies Affected Cases in Spain and Their Therapeutic and Extended Epidemiological Implications. Sci. Rep. 2021, 11, 1526. [Google Scholar] [CrossRef] [PubMed]
  92. Parmeggiani, F.S.; Sorrentino, F.; Ponzin, D.; Barbaro, V.; Ferrari, S.; Di Iorio, E. Retinitis Pigmentosa: Genes and Disease Mechanisms. Curr. Genom. 2011, 12, 238–249. [Google Scholar] [CrossRef]
  93. Palczewski, K. Chemistry and Biology of Vision. J. Biol. Chem. 2012, 287, 1612–1619. [Google Scholar] [CrossRef][Green Version]
  94. Lenahan, C.; Sanghavi, R.; Huang, L.; Zhang, J.H. Rhodopsin: A Potential Biomarker for Neurodegenerative Diseases. Front. Neurosci. 2020, 14, 326. [Google Scholar] [CrossRef][Green Version]
  95. Kandori, H.; Shichida, Y.; Yoshizawa, T. Photoisomerization in Rhodopsin. Biochemistry 2001, 66, 1197–1209. [Google Scholar] [CrossRef]
  96. Palczewski, K. G Protein-Coupled Receptor Rhodopsin. Annu. Rev. Biochem. 2006, 75, 743–767. [Google Scholar] [CrossRef][Green Version]
  97. Kramer, R.H.; Molokanova, E. Modulation of Cyclic-Nucleotide-Gated Channels and Regulation of Vertebrate Phototransduction. J. Exp. Biol. 2001, 204, 2921–2931. [Google Scholar] [CrossRef] [PubMed]
  98. BIO254: Phototransduction—OpenWetWare. Available online: https://openwetware.org/mediawiki/index.php?title=BIO254:Phototransduction&oldid=85424 (accessed on 12 February 2023).
  99. Newton, F.; Megaw, R. Mechanisms of Photoreceptor Death in Retinitis Pigmentosa. Genes 2020, 11, 1120. [Google Scholar] [CrossRef]
  100. Choudhury, S.; Bhootada, Y.; Gorbatyuk, O.; Gorbatyuk, M. Caspase-7 Ablation Modulates UPR, Reprograms TRAF2-JNK Apoptosis and Protects T17M Rhodopsin Mice from Severe Retinal Degeneration. Cell Death Dis. 2013, 4, e528. [Google Scholar] [CrossRef] [PubMed][Green Version]
  101. Comitato, A.; Sanges, D.; Rossi, A.; Humphries, M.M.; Marigo, V. Activation of Bax in Three Models of Retinitis Pigmentosa. Investig. Ophthalmol. Vis. Sci. 2014, 55, 3555. [Google Scholar] [CrossRef] [PubMed][Green Version]
  102. Kulbay, M.; Paimboeuf, A.; Ozdemir, D.; Bernier, J. Review of Cancer Cell Resistance Mechanisms to Apoptosis and Actual Targeted Therapies. J. Cell. Biochem. 2022, 123, 1736–1761. [Google Scholar] [CrossRef]
  103. Zhao, L.; Hou, C.; Yan, N. Neuroinflammation in Retinitis Pigmentosa: Therapies Targeting the Innate Immune System. Front. Immunol. 2022, 13, 1059947. [Google Scholar] [CrossRef] [PubMed]
  104. Read, A.; Schröder, M. The Unfolded Protein Response: An Overview. Biology 2021, 10, 384. [Google Scholar] [CrossRef]
  105. Junjappa, R.P.; Patil, P.; Bhattarai, K.R.; Kim, H.-R.; Chae, H.-J. IRE1α Implications in Endoplasmic Reticulum Stress-Mediated Development and Pathogenesis of Autoimmune Diseases. Front. Immunol. 2018, 9, 1289. [Google Scholar] [CrossRef][Green Version]
  106. Teske, B.F.; Wek, S.A.; Bunpo, P.; Cundiff, J.K.; McClintick, J.N.; Anthony, T.G.; Wek, R.C. The EIF2 Kinase PERK and the Integrated Stress Response Facilitate Activation of ATF6 during Endoplasmic Reticulum Stress. Mol. Biol. Cell 2011, 22, 4390–4405. [Google Scholar] [CrossRef]
  107. Hillary, R.F.; FitzGerald, U. A Lifetime of Stress: ATF6 in Development and Homeostasis. J. Biomed. Sci. 2018, 25, 48. [Google Scholar] [CrossRef][Green Version]
  108. Wang, M.; Wey, S.; Zhang, Y.; Ye, R.; Lee, A.S. Role of the Unfolded Protein Response Regulator GRP78/BiP in Development, Cancer, and Neurological Disorders. Antioxid. Redox Signal. 2009, 11, 2307–2316. [Google Scholar] [CrossRef] [PubMed][Green Version]
  109. Dhuriya, Y.K.; Sharma, D. Necroptosis: A Regulated Inflammatory Mode of Cell Death. J. Neuroinflammation 2018, 15, 199. [Google Scholar] [CrossRef] [PubMed][Green Version]
  110. Daiger, S.P.; Bowne, S.J.; Sullivan, L.S. Genes and Mutations Causing Autosomal Dominant Retinitis Pigmentosa. Cold Spring Harb. Perspect. Med. 2014, 5, a017129. [Google Scholar] [CrossRef] [PubMed][Green Version]
  111. Massengill, M.T.; Lewin, A.S. Gene Therapy for Rhodopsin-Associated Autosomal Dominant Retinitis Pigmentosa. Int. Ophthalmol. Clin. 2021, 61, 79–96. [Google Scholar] [CrossRef] [PubMed]
  112. Li, T.; Snyder, W.K.; Olsson, J.E.; Dryja, T.P. Transgenic Mice Carrying the Dominant Rhodopsin Mutation P347S: Evidence for Defective Vectorial Transport of Rhodopsin to the Outer Segments. Proc. Natl. Acad. Sci. USA 1996, 93, 14176–14181. [Google Scholar] [CrossRef] [PubMed][Green Version]
  113. Kraft, T.W.; Allen, D.; Petters, R.M.; Hao, Y.; Peng, Y.-W.; Wong, F. Altered Light Responses of Single Rod Photoreceptors in Transgenic Pigs Expressing P347L or P347S Rhodopsin. Mol. Vis. 2005, 11, 1246–1256. [Google Scholar] [PubMed]
  114. Mussolino, C.; Sanges, D.; Marrocco, E.; Bonetti, C.; Di Vicino, U.; Marigo, V.; Auricchio, A.; Meroni, G.; Surace, E.M. Zinc-Finger-Based Transcriptional Repression of Rhodopsin in a Model of Dominant Retinitis Pigmentosa. EMBO Mol. Med. 2011, 3, 118–128. [Google Scholar] [CrossRef][Green Version]
  115. Chadderton, N.; Millington-Ward, S.; Palfi, A.; O’Reilly, M.; Tuohy, G.; Humphries, M.M.; Li, T.; Humphries, P.; Kenna, P.F.; Farrar, G.J. Improved Retinal Function in a Mouse Model of Dominant Retinitis Pigmentosa Following AAV-Delivered Gene Therapy. Mol. Ther. 2009, 17, 593–599. [Google Scholar] [CrossRef]
  116. Palfi, A.; Millington-Ward, S.; Chadderton, N.; O’Reilly, M.; Goldmann, T.; Humphries, M.M.; Li, T.; Wolfrum, U.; Humphries, P.; Kenna, P.F.; et al. Adeno-Associated Virus-Mediated Rhodopsin Replacement Provides Therapeutic Benefit in Mice with a Targeted Disruption of the Rhodopsin Gene. Hum. Gene Ther. 2010, 21, 311–323. [Google Scholar] [CrossRef]
  117. Millington-Ward, S.; Chadderton, N.; O’Reilly, M.; Palfi, A.; Goldmann, T.; Kilty, C.; Humphries, M.; Wolfrum, U.; Bennett, J.; Humphries, P.; et al. Suppression and Replacement Gene Therapy for Autosomal Dominant Disease in a Murine Model of Dominant Retinitis Pigmentosa. Mol. Ther. 2011, 19, 642–649. [Google Scholar] [CrossRef]
  118. Moore, S.M.; Skowronska-Krawczyk, D.; Chao, D.L. Targeting of the NRL Pathway as a Therapeutic Strategy to Treat Retinitis Pigmentosa. J. Clin. Med. 2020, 9, 2224. [Google Scholar] [CrossRef] [PubMed]
  119. Conte, I.; Hadfield, K.D.; Barbato, S.; Carrella, S.; Pizzo, M.; Bhat, R.S.; Carissimo, A.; Karali, M.; Porter, L.F.; Urquhart, J.; et al. MiR-204 Is Responsible for Inherited Retinal Dystrophy Associated with Ocular Coloboma. Proc. Natl. Acad. Sci. USA 2015, 112, E3236–E3245. [Google Scholar] [CrossRef] [PubMed][Green Version]
  120. Piano, I.; D’Antongiovanni, V.; Novelli, E.; Biagioni, M.; Dei Cas, M.; Paroni, R.C.; Ghidoni, R.; Strettoi, E.; Gargini, C. Myriocin Effect on Tvrm4 Retina, an Autosomal Dominant Pattern of Retinitis Pigmentosa. Front. Neurosci. 2020, 14, 372. [Google Scholar] [CrossRef] [PubMed]
  121. Jiang, H.; Xiong, S.; Xia, X. Retinitis Pigmentosa-Associated Rhodopsin Mutant T17M Induces Endoplasmic Reticulum (ER) Stress and Sensitizes Cells to ER Stress-Induced Cell Death. Mol. Med. Rep. 2014, 9, 1737–1742. [Google Scholar] [CrossRef][Green Version]
  122. Bhootada, Y.; Gully, C.; Gorbatyuk, M.S. Controlling PERK-ATF4-CHOP Branch of the UPR Is the Key to Reverse Retinal Degeneration of T17M Retina. Investig. Ophthalmol. Vis. Sci. 2015, 56, 5409. [Google Scholar]
  123. Yang, C.; Georgiou, M.; Atkinson, R.; Collin, J.; Al-Aama, J.; Nagaraja-Grellscheid, S.; Johnson, C.; Ali, R.; Armstrong, L.; Mozaffari-Jovin, S.; et al. Pre-MRNA Processing Factors and Retinitis Pigmentosa: RNA Splicing and Beyond. Front. Cell Dev. Biol. 2021, 9, 700276. [Google Scholar] [CrossRef]
  124. Bowne, S. Mutations in the RP1 Gene Causing Autosomal Dominant Retinitis Pigmentosa. Hum. Mol. Genet. 1999, 8, 2121–2128. [Google Scholar] [CrossRef][Green Version]
  125. Liu, Q.; Zhou, J.; Daiger, S.P.; Farber, D.B.; Heckenlively, J.R.; Smith, J.E.; Sullivan, L.S.; Zuo, J.; Milam, A.H.; Pierce, E.A. Identification and Subcellular Localization of the RP1 Protein in Human and Mouse Photoreceptors. Investig. Ophthalmol. Vis. Sci. 2002, 43, 22–32. [Google Scholar]
  126. Liu, Q.; Saveliev, A.; Hu, J.; Cao, H.; Auricchio, A.; Pierce, E.A. The Degeneration of Photoreceptor Cells in the Rp1 Form of Retinitis Pigmentosa Is Caused by a Dominant Mechanism. Investig. Ophthalmol. Vis. Sci. 2009, 50, 2285. [Google Scholar]
  127. Athanasiou, D.; Aguila, M.; Bellingham, J.; Li, W.; McCulley, C.; Reeves, P.J.; Cheetham, M.E. The Molecular and Cellular Basis of Rhodopsin Retinitis Pigmentosa Reveals Potential Strategies for Therapy. Prog. Retin. Eye Res. 2018, 62, 1–23. [Google Scholar] [CrossRef][Green Version]
  128. Saqib, M.A.N.; Nikopoulos, K.; Ullah, E.; Sher Khan, F.; Iqbal, J.; Bibi, R.; Jarral, A.; Sajid, S.; Nishiguchi, K.M.; Venturini, G.; et al. Homozygosity Mapping Reveals Novel and Known Mutations in Pakistani Families with Inherited Retinal Dystrophies. Sci. Rep. 2015, 5, 9965. [Google Scholar] [CrossRef] [PubMed][Green Version]
  129. Van Schil, K.; Karlstetter, M.; Aslanidis, A.; Dannhausen, K.; Azam, M.; Qamar, R.; Leroy, B.P.; Depasse, F.; Langmann, T.; De Baere, E. Autosomal Recessive Retinitis Pigmentosa with Homozygous Rhodopsin Mutation E150K and Non-Coding Cis-Regulatory Variants in CRX-Binding Regions of SAMD7. Sci. Rep. 2016, 6, 21307. [Google Scholar] [CrossRef] [PubMed][Green Version]
  130. Zhang, N.; Kolesnikov, A.V.; Jastrzebska, B.; Mustafi, D.; Sawada, O.; Maeda, T.; Genoud, C.; Engel, A.; Kefalov, V.J.; Palczewski, K. Autosomal Recessive Retinitis Pigmentosa E150K Opsin Mice Exhibit Photoreceptor Disorganization. J. Clin. Investig. 2013, 123, 121–137. [Google Scholar] [CrossRef] [PubMed][Green Version]
  131. Collin, R.W.J.; van den Born, L.I.; Klevering, B.J.; de Castro-Miró, M.; Littink, K.W.; Arimadyo, K.; Azam, M.; Yazar, V.; Zonneveld, M.N.; Paun, C.C.; et al. High-Resolution Homozygosity Mapping Is a Powerful Tool to Detect Novel Mutations Causative of Autosomal Recessive RP in the Dutch Population. Investig. Ophthalmol. Vis. Sci. 2011, 52, 2227. [Google Scholar] [CrossRef][Green Version]
  132. Nassisi, M.; Smirnov, V.M.; Solis Hernandez, C.; Mohand-Saïd, S.; Condroyer, C.; Antonio, A.; Kühlewein, L.; Kempf, M.; Kohl, S.; Wissinger, B.; et al. CNGB1-related Rod-cone Dystrophy: A Mutation Review and Update. Hum. Mutat. 2021, 42, 641–666. [Google Scholar] [CrossRef] [PubMed]
  133. Jacobson, S.G.; Cideciyan, A.V.; Huang, W.C.; Sumaroka, A.; Roman, A.J.; Schwartz, S.B.; Luo, X.; Sheplock, R.; Dauber, J.M.; Swider, M.; et al. TULP1 Mutations Causing Early-Onset Retinal Degeneration: Preserved but Insensitive Macular Cones. Investig. Ophthalmol. Vis. Sci. 2014, 55, 5354. [Google Scholar] [CrossRef][Green Version]
  134. Chhetri, J.; Jacobson, G.; Gueven, N. Zebrafish—On the Move towards Ophthalmological Research. Eye 2014, 28, 367–380. [Google Scholar] [CrossRef][Green Version]
  135. Martinez-Fernandez De La Camara, C.; Nanda, A.; Salvetti, A.P.; Fischer, M.D.; MacLaren, R.E. Gene Therapy for the Treatment of X-Linked Retinitis Pigmentosa. Expert Opin. Orphan Drugs 2018, 6, 167–177. [Google Scholar] [CrossRef][Green Version]
  136. Koyanagi, Y.; Akiyama, M.; Nishiguchi, K.M.; Momozawa, Y.; Kamatani, Y.; Takata, S.; Inai, C.; Iwasaki, Y.; Kumano, M.; Murakami, Y.; et al. Genetic Characteristics of Retinitis Pigmentosa in 1204 Japanese Patients. J. Med. Genet. 2019, 56, 662–670. [Google Scholar] [CrossRef]
  137. González-del Pozo, M.; Fernández-Suárez, E.; Martín-Sánchez, M.; Bravo-Gil, N.; Méndez-Vidal, C.; Rodríguez-de la Rúa, E.; Borrego, S.; Antiñolo, G. Unmasking Retinitis Pigmentosa Complex Cases by a Whole Genome Sequencing Algorithm Based on Open-Access Tools: Hidden Recessive Inheritance and Potential Oligogenic Variants. J. Transl. Med. 2020, 18, 73. [Google Scholar] [CrossRef][Green Version]
  138. Birtel, J.; Gliem, M.; Mangold, E.; Müller, P.L.; Holz, F.G.; Neuhaus, C.; Lenzner, S.; Zahnleiter, D.; Betz, C.; Eisenberger, T.; et al. Next-Generation Sequencing Identifies Unexpected Genotype-Phenotype Correlations in Patients with Retinitis Pigmentosa. PLoS ONE 2018, 13, e0207958. [Google Scholar] [CrossRef] [PubMed][Green Version]
  139. Millo, T.; Rivera, A.; Obolensky, A.; Marks-Ohana, D.; Xu, M.; Li, Y.; Wilhelm, E.; Gopalakrishnan, P.; Gross, M.; Rosin, B.; et al. Identification of Autosomal Recessive Novel Genes and Retinal Phenotypes in Members of the Solute Carrier (SLC) Superfamily. Genet. Med. 2022, 24, 1523–1535. [Google Scholar] [CrossRef] [PubMed]
  140. Jin, Z.-B.; Huang, X.-F.; Lv, J.-N.; Xiang, L.; Li, D.-Q.; Chen, J.; Huang, C.; Wu, J.; Lu, F.; Qu, J. SLC7A14 Linked to Autosomal Recessive Retinitis Pigmentosa. Nat. Commun. 2014, 5, 3517. [Google Scholar] [CrossRef] [PubMed][Green Version]
  141. Branham, K.; Matsui, H.; Biswas, P.; Guru, A.A.; Hicks, M.; Suk, J.J.; Li, H.; Jakubosky, D.; Long, T.; Telenti, A.; et al. Establishing the Involvement of the Novel Gene AGBL5 in Retinitis Pigmentosa by Whole Genome Sequencing. Physiol. Genom. 2016, 48, 922–927. [Google Scholar] [CrossRef] [PubMed][Green Version]
  142. Jindal, N.; Banik, A.; Prabhakar, S.; Vaiphie, K.; Anand, A. Alteration of Neurotrophic Factors After Transplantation of Bone Marrow Derived Lin-ve Stem Cell in NMDA-Induced Mouse Model of Retinal Degeneration. J. Cell. Biochem. 2017, 118, 1699–1711. [Google Scholar] [CrossRef]
  143. Kashani, A.H.; Uang, J.; Mert, M.; Rahhal, F.; Chan, C.; Avery, R.L.; Dugel, P.; Chen, S.; Lebkowski, J.; Clegg, D.O.; et al. Surgical Method for Implantation of a Biosynthetic Retinal Pigment Epithelium Monolayer for Geographic Atrophy: Experience from a Phase 1/2a Study. Ophthalmol. Retin. 2020, 4, 264–273. [Google Scholar] [CrossRef]
  144. Mandai, M.; Fujii, M.; Hashiguchi, T.; Sunagawa, G.A.; Ito, S.; Sun, J.; Kaneko, J.; Sho, J.; Yamada, C.; Takahashi, M. IPSC-Derived Retina Transplants Improve Vision in Rd1 End-Stage Retinal-Degeneration Mice. Stem Cell Rep. 2017, 8, 69–83. [Google Scholar] [CrossRef][Green Version]
  145. Salas, A.; Duarri, A.; Fontrodona, L.; Ramírez, D.M.; Badia, A.; Isla-Magrané, H.; Ferreira-de-Souza, B.; Zapata, M.Á.; Raya, Á.; Veiga, A.; et al. Cell Therapy with HiPSC-Derived RPE Cells and RPCs Prevents Visual Function Loss in a Rat Model of Retinal Degeneration. Mol. Ther.-Methods Clin. Dev. 2021, 20, 688–702. [Google Scholar] [CrossRef]
  146. Surendran, H.; Nandakumar, S.; Reddy, K.V.B.; Stoddard, J.; Mohan, K.V.; Upadhyay, P.K.; McGill, T.J.; Pal, R. Transplantation of Retinal Pigment Epithelium and Photoreceptors Generated Concomitantly via Small Molecule-Mediated Differentiation Rescues Visual Function in Rodent Models of Retinal Degeneration. Stem Cell Res. Ther. 2021, 12, 70. [Google Scholar] [CrossRef]
  147. Lin, B.; McLelland, B.T.; Aramant, R.B.; Thomas, B.B.; Nistor, G.; Keirstead, H.S.; Seiler, M.J. Retina Organoid Transplants Develop Photoreceptors and Improve Visual Function in RCS Rats With RPE Dysfunction. Investig. Ophthalmol. Vis. Sci. 2020, 61, 34. [Google Scholar] [CrossRef]
  148. Duarri, A.; Rodríguez-Bocanegra, E.; Martínez-Navarrete, G.; Biarnés, M.; García, M.; Ferraro, L.L.; Kuebler, B.; Aran, B.; Izquierdo, E.; Aguilera-Xiol, E.; et al. Transplantation of Human Induced Pluripotent Stem Cell-Derived Retinal Pigment Epithelium in a Swine Model of Geographic Atrophy. Int. J. Mol. Sci. 2021, 22, 10497. [Google Scholar] [CrossRef] [PubMed]
  149. Thomas, B.B.; Lin, B.; Martinez-Camarillo, J.C.; Zhu, D.; McLelland, B.T.; Nistor, G.; Keirstead, H.S.; Humayun, M.S.; Seiler, M.J. Co-Grafts of Human Embryonic Stem Cell Derived Retina Organoids and Retinal Pigment Epithelium for Retinal Reconstruction in Immunodeficient Retinal Degenerate Royal College of Surgeons Rats. Front. Neurosci. 2021, 15, 752958. [Google Scholar] [CrossRef] [PubMed]
  150. Ferroni, L.; Gardin, C.; Tocco, I.; Epis, R.; Casadei, A.; Vindigni, V.; Mucci, G.; Zavan, B. Potential for Neural Differentiation of Mesenchymal Stem Cells. Adv. Biochem. Eng. Biotechnol. 2013, 129, 89–115. [Google Scholar] [CrossRef]
  151. Bassi, Ê.J.; de Almeida, D.C.; Moraes-Vieira, P.M.M.; Câmara, N.O.S. Exploring the Role of Soluble Factors Associated with Immune Regulatory Properties of Mesenchymal Stem Cells. Stem Cell Rev. Rep. 2012, 8, 329–342. [Google Scholar] [CrossRef] [PubMed]
  152. Soleymaninejadian, E.; Pramanik, K.; Samadian, E. Immunomodulatory Properties of Mesenchymal Stem Cells: Cytokines and Factors. Am. J. Reprod. Immunol. 2012, 67, 1–8. [Google Scholar] [CrossRef][Green Version]
  153. Ding, S.L.S.; Kumar, S.; Mok, P.L. Cellular Reparative Mechanisms of Mesenchymal Stem Cells for Retinal Diseases. Int. J. Mol. Sci. 2017, 18, 1406. [Google Scholar] [CrossRef][Green Version]
  154. Brown, C.; Agosta, P.; McKee, C.; Walker, K.; Mazzella, M.; Alamri, A.; Svinarich, D.; Chaudhry, G.R. Human Primitive Mesenchymal Stem Cell-Derived Retinal Progenitor Cells Improved Neuroprotection, Neurogenesis, and Vision in Rd12 Mouse Model of Retinitis Pigmentosa. Stem Cell Res. Ther. 2022, 13, 148. [Google Scholar] [CrossRef]
  155. Kolomeyer, A.M.; Zarbin, M.A. Trophic Factors in the Pathogenesis and Therapy for Retinal Degenerative Diseases. Surv. Ophthalmol. 2014, 59, 134–165. [Google Scholar] [CrossRef]
  156. Talcott, K.E.; Ratnam, K.; Sundquist, S.M.; Lucero, A.S.; Lujan, B.J.; Tao, W.; Porco, T.C.; Roorda, A.; Duncan, J.L. Longitudinal Study of Cone Photoreceptors during Retinal Degeneration and in Response to Ciliary Neurotrophic Factor Treatment. Investig. Ophthalmol. Vis. Sci. 2011, 52, 2219. [Google Scholar] [CrossRef]
  157. Moisseiev, E.; Smit-McBride, Z.; Oltjen, S.; Zhang, P.; Zawadzki, R.J.; Motta, M.; Murphy, C.J.; Cary, W.; Annett, G.; Nolta, J.A.; et al. Intravitreal Administration of Human Bone Marrow CD34+ Stem Cells in a Murine Model of Retinal Degeneration. Investig. Ophthalmol. Vis. Sci. 2016, 57, 4125. [Google Scholar] [CrossRef]
  158. Soleimannejad, M.; Ebrahimi-Barough, S.; Nadri, S.; Riazi-Esfahani, M.; Soleimani, M.; Tavangar, S.M.; Ai, J. Retina Tissue Engineering by Conjunctiva Mesenchymal Stem Cells Encapsulated in Fibrin Gel: Hypotheses on Novel Approach to Retinal Diseases Treatment. Med. Hypotheses 2017, 101, 75–77. [Google Scholar] [CrossRef] [PubMed]
  159. Zhang, J.; Li, P.; Zhao, G.; He, S.; Xu, D.; Jiang, W.; Peng, Q.; Li, Z.; Xie, Z.; Zhang, H.; et al. Mesenchymal Stem Cell-Derived Extracellular Vesicles Protect Retina in a Mouse Model of Retinitis Pigmentosa by Anti-Inflammation through MiR-146a-Nr4a3 Axis. Stem Cell Res. Ther. 2022, 13, 394. [Google Scholar] [CrossRef] [PubMed]
  160. Pan, T.; Shen, H.; Yuan, S.; Lu, G.; Zhang, Y.; Wang, H.; Zhao, Y.; Sun, X.; Liu, Q. Combined Transplantation With Human Mesenchymal Stem Cells Improves Retinal Rescue Effect of Human Fetal RPE Cells in Retinal Degeneration Mouse Model. Investig. Ophthalmol. Vis. Sci. 2020, 61, 9. [Google Scholar] [CrossRef] [PubMed]
  161. Wang, N.-K.; Tosi, J.; Kasanuki, J.M.; Chou, C.L.; Kong, J.; Parmalee, N.; Wert, K.J.; Allikmets, R.; Lai, C.-C.; Chien, C.-L.; et al. Transplantation of Reprogrammed Embryonic Stem Cells Improves Visual Function in a Mouse Model for Retinitis Pigmentosa. Transplantation 2010, 89, 911–919. [Google Scholar] [CrossRef]
  162. Klassen, H.J.; Ng, T.F.; Kurimoto, Y.; Kirov, I.; Shatos, M.; Coffey, P.; Young, M.J. Multipotent Retinal Progenitors Express Developmental Markers, Differentiate into Retinal Neurons, and Preserve Light-Mediated Behavior. Investig. Ophthalmol. Vis. Sci. 2004, 45, 4167. [Google Scholar] [CrossRef]
  163. Qiu, G.; Seiler, M.J.; Thomas, B.B.; Wu, K.; Radosevich, M.; Sadda, S.R. Revisiting Nestin Expression in Retinal Progenitor Cells in Vitro and after Transplantation in Vivo. Exp. Eye Res. 2007, 84, 1047–1059. [Google Scholar] [CrossRef][Green Version]
  164. MacLaren, R.E.; Pearson, R.A.; MacNeil, A.; Douglas, R.H.; Salt, T.E.; Akimoto, M.; Swaroop, A.; Sowden, J.C.; Ali, R.R. Retinal Repair by Transplantation of Photoreceptor Precursors. Nature 2006, 444, 203–207. [Google Scholar] [CrossRef]
  165. He, X.-Y.; Zhao, C.-J.; Xu, H.; Chen, K.; Bian, B.-S.-J.; Gong, Y.; Weng, C.-H.; Zeng, Y.-X.; Fu, Y.; Liu, Y.; et al. Synaptic Repair and Vision Restoration in Advanced Degenerating Eyes by Transplantation of Retinal Progenitor Cells. Stem Cell Rep. 2021, 16, 1805–1817. [Google Scholar] [CrossRef]
  166. Stern, J.H.; Tian, Y.; Funderburgh, J.; Pellegrini, G.; Zhang, K.; Goldberg, J.L.; Ali, R.R.; Young, M.; Xie, Y.; Temple, S. Regenerating Eye Tissues to Preserve and Restore Vision. Cell Stem Cell 2018, 22, 834–849. [Google Scholar] [CrossRef][Green Version]
  167. Ellingford, J.M.; Barton, S.; Bhaskar, S.; O’Sullivan, J.; Williams, S.G.; Lamb, J.A.; Panda, B.; Sergouniotis, P.I.; Gillespie, R.L.; Daiger, S.P.; et al. Molecular Findings from 537 Individuals with Inherited Retinal Disease. J. Med. Genet. 2016, 53, 761–767. [Google Scholar] [CrossRef][Green Version]
  168. Bi, A.; Cui, J.; Ma, Y.-P.; Olshevskaya, E.; Pu, M.; Dizhoor, A.M.; Pan, Z.-H. Ectopic Expression of a Microbial-Type Rhodopsin Restores Visual Responses in Mice with Photoreceptor Degeneration. Neuron 2006, 50, 23–33. [Google Scholar] [CrossRef] [PubMed][Green Version]
  169. Tomita, H.; Sugano, E.; Fukazawa, Y.; Isago, H.; Sugiyama, Y.; Hiroi, T.; Ishizuka, T.; Mushiake, H.; Kato, M.; Hirabayashi, M.; et al. Visual Properties of Transgenic Rats Harboring the Channelrhodopsin-2 Gene Regulated by the Thy-1.2 Promoter. PLoS ONE 2009, 4, e7679. [Google Scholar] [CrossRef] [PubMed][Green Version]
  170. Simon, C.-J.; Sahel, J.-A.; Duebel, J.; Herlitze, S.; Dalkara, D. Opsins for Vision Restoration. Biochem. Biophys. Res. Commun. 2020, 527, 325–330. [Google Scholar] [CrossRef] [PubMed]
  171. Zhang, F.; Vierock, J.; Yizhar, O.; Fenno, L.E.; Tsunoda, S.; Kianianmomeni, A.; Prigge, M.; Berndt, A.; Cushman, J.; Polle, J.; et al. The Microbial Opsin Family of Optogenetic Tools. Cell 2011, 147, 1446–1457. [Google Scholar] [CrossRef] [PubMed][Green Version]
  172. Deisseroth, K. Optogenetics: 10 Years of Microbial Opsins in Neuroscience. Nat. Neurosci. 2015, 18, 1213–1225. [Google Scholar] [CrossRef][Green Version]
  173. Gradinaru, V.; Zhang, F.; Ramakrishnan, C.; Mattis, J.; Prakash, R.; Diester, I.; Goshen, I.; Thompson, K.R.; Deisseroth, K. Molecular and Cellular Approaches for Diversifying and Extending Optogenetics. Cell 2010, 141, 154–165. [Google Scholar] [CrossRef][Green Version]
  174. Bedbrook, C.N.; Yang, K.K.; Rice, A.J.; Gradinaru, V.; Arnold, F.H. Machine Learning to Design Integral Membrane Channelrhodopsins for Efficient Eukaryotic Expression and Plasma Membrane Localization. PLoS Comput. Biol. 2017, 13, e1005786. [Google Scholar] [CrossRef][Green Version]
  175. Garita-Hernandez, M.; Guibbal, L.; Toualbi, L.; Routet, F.; Chaffiol, A.; Winckler, C.; Harinquet, M.; Robert, C.; Fouquet, S.; Bellow, S.; et al. Optogenetic Light Sensors in Human Retinal Organoids. Front. Neurosci. 2018, 12, 789. [Google Scholar] [CrossRef][Green Version]
  176. Gaub, B.M.; Berry, M.H.; Holt, A.E.; Reiner, A.; Kienzler, M.A.; Dolgova, N.; Nikonov, S.; Aguirre, G.D.; Beltran, W.A.; Flannery, J.G.; et al. Restoration of Visual Function by Expression of a Light-Gated Mammalian Ion Channel in Retinal Ganglion Cells or ON-Bipolar Cells. Proc. Natl. Acad. Sci. USA 2014, 111, E5574–E5583. [Google Scholar] [CrossRef][Green Version]
  177. Ameline, B.; Tshilenge, K.-T.; Weber, M.; Biget, M.; Libeau, L.; Caplette, R.; Mendes-Madeira, A.; Provost, N.; Guihal, C.; Picaud, S.; et al. Long-Term Expression of Melanopsin and Channelrhodopsin Causes No Gross Alterations in the Dystrophic Dog Retina. Gene Ther. 2017, 24, 735–741. [Google Scholar] [CrossRef]
  178. Nikonov, S.; Aravand, P.; Lyubarsky, A.; Nikonov, R.; Luo, A.J.; Wei, Z.; Maguire, A.M.; Phelps, N.T.; Shpylchak, I.; Willett, K.; et al. Restoration of Vision and Retinal Responses After Adeno-Associated Virus–Mediated Optogenetic Therapy in Blind Dogs. Transl. Vis. Sci. Technol. 2022, 11, 24. [Google Scholar] [CrossRef] [PubMed]
  179. Chaffiol, A.; Caplette, R.; Jaillard, C.; Brazhnikova, E.; Desrosiers, M.; Dubus, E.; Duhamel, L.; Macé, E.; Marre, O.; Benoit, P.; et al. A New Promoter Allows Optogenetic Vision Restoration with Enhanced Sensitivity in Macaque Retina. Mol. Ther. 2017, 25, 2546–2560. [Google Scholar] [CrossRef] [PubMed][Green Version]
  180. Ganjawala, T.H.; Lu, Q.; Fenner, M.D.; Abrams, G.W.; Pan, Z.-H. Improved CoChR Variants Restore Visual Acuity and Contrast Sensitivity in a Mouse Model of Blindness under Ambient Light Conditions. Mol. Ther. 2019, 27, 1195–1205. [Google Scholar] [CrossRef] [PubMed]
  181. Tabata, K.; Sugano, E.; Hatakeyama, A.; Watanabe, Y.; Suzuki, T.; Ozaki, T.; Fukuda, T.; Tomita, H. Phototoxicities Caused by Continuous Light Exposure Were Not Induced in Retinal Ganglion Cells Transduced by an Optogenetic Gene. Int. J. Mol. Sci. 2021, 22, 6732. [Google Scholar] [CrossRef]
  182. Watanabe, Y.; Sugano, E.; Tabata, K.; Hatakeyama, A.; Sakajiri, T.; Fukuda, T.; Ozaki, T.; Suzuki, T.; Sayama, T.; Tomita, H. Development of an Optogenetic Gene Sensitive to Daylight and Its Implications in Vision Restoration. Npj Regen. Med. 2021, 6, 64. [Google Scholar] [CrossRef]
  183. Weis, W.I.; Kobilka, B.K. The Molecular Basis of G Protein-Coupled Receptor Activation. Annu. Rev. Biochem. 2018, 87, 897–919. [Google Scholar] [CrossRef]
  184. Katada, Y.; Yoshida, K.; Serizawa, N.; Kobayashi, K.; Neghisi, K.; Okano, H.; Kandori, H.; Tsubota, K.; Kurihara, T. High-Sensitivity Vision Restoration via Ectopic Expression of Chimeric Rhodopsin in Mice. bioRxiv 2020. [CrossRef]
  185. Buch, P.; MacLaren, R.; Ali, R. Neuroprotective Gene Therapy for the Treatment of Inherited Retinal Degeneration. Curr. Gene Ther. 2007, 7, 434–445. [Google Scholar] [CrossRef]
  186. Delplace, V.; Ortin-Martinez, A.; Tsai, E.L.S.; Amin, A.N.; Wallace, V.; Shoichet, M.S. Controlled Release Strategy Designed for Intravitreal Protein Delivery to the Retina. J. Control. Release 2019, 293, 10–20. [Google Scholar] [CrossRef]
  187. Gupta, V.; You, Y.; Gupta, V.; Klistorner, A.; Graham, S. TrkB Receptor Signalling: Implications in Neurodegenerative, Psychiatric and Proliferative Disorders. Int. J. Mol. Sci. 2013, 14, 10122–10142. [Google Scholar] [CrossRef][Green Version]
  188. Pardue, M.T.; Allen, R.S. Neuroprotective Strategies for Retinal Disease. Prog. Retin. Eye Res. 2018, 65, 50–76. [Google Scholar] [CrossRef] [PubMed]
  189. Wen, R.; Tao, W.; Li, Y.; Sieving, P.A. CNTF and Retina. Prog. Retin. Eye Res. 2012, 31, 136–151. [Google Scholar] [CrossRef] [PubMed][Green Version]
  190. Ghasemi, M.; Alizadeh, E.; Saei Arezoumand, K.; Fallahi Motlagh, B.; Zarghami, N. Ciliary Neurotrophic Factor (CNTF) Delivery to Retina: An Overview of Current Research Advancements. Artif. Cells Nanomed. Biotechnol. 2017, 46, 1694–1707. [Google Scholar] [CrossRef]
  191. Chew, E.Y.; Clemons, T.E.; Jaffe, G.J.; Johnson, C.A.; Farsiu, S.; Lad, E.M.; Guymer, R.; Rosenfeld, P.; Hubschman, J.-P.; Constable, I.; et al. Effect of Ciliary Neurotrophic Factor on Retinal Neurodegeneration in Patients with Macular Telangiectasia Type 2. Ophthalmology 2019, 126, 540–549. [Google Scholar] [CrossRef] [PubMed]
  192. Bielmeier, C.B.; Roth, S.; Schmitt, S.I.; Boneva, S.K.; Schlecht, A.; Vallon, M.; Tamm, E.R.; Ergün, S.; Neueder, A.; Braunger, B.M. Transcriptional Profiling Identifies Upregulation of Neuroprotective Pathways in Retinitis Pigmentosa. Int. J. Mol. Sci. 2021, 22, 6307. [Google Scholar] [CrossRef] [PubMed]
  193. Bramall, A.N.; Szego, M.J.; Pacione, L.R.; Chang, I.; Diez, E.; D’Orleans-Juste, P.; Stewart, D.J.; Hauswirth, W.W.; Yanagisawa, M.; McInnes, R.R. Endothelin-2-Mediated Protection of Mutant Photoreceptors in Inherited Photoreceptor Degeneration. PLoS ONE 2013, 8, e58023. [Google Scholar] [CrossRef][Green Version]
  194. Froger, N.; Matonti, F.; Roubeix, C.; Forster, V.; Ivkovic, I.; Brunel, N.; Baudouin, C.; Sahel, J.-A.; Picaud, S. VEGF Is an Autocrine/Paracrine Neuroprotective Factor for Injured Retinal Ganglion Neurons. Sci. Rep. 2020, 10, 12409. [Google Scholar] [CrossRef]
  195. Tao, W.; Wen, R.; Goddard, M.B.; Sherman, S.D.; O’Rourke, P.J.; Stabila, P.F.; Bell, W.J.; Dean, B.J.; Kauper, K.A.; Budz, V.A.; et al. Encapsulated Cell-Based Delivery of CNTF Reduces Photoreceptor Degeneration in Animal Models of Retinitis Pigmentosa. Investig. Ophthalmol. Vis. Sci. 2002, 43, 3292–3298. [Google Scholar]
  196. Yang, J.-Y.; Lu, B.; Feng, Q.; Alfaro, J.S.; Chen, P.-H.; Loscalzo, J.; Wei, W.-B.; Zhang, Y.-Y.; Lu, S.-J.; Wang, S. Retinal Protection by Sustained Nanoparticle Delivery of Oncostatin M and Ciliary Neurotrophic Factor Into Rodent Models of Retinal Degeneration. Transl. Vis. Sci. Technol. 2021, 10, 6. [Google Scholar] [CrossRef]
  197. Fernández-Sánchez, L.; Lax, P.; Pinilla, I.; Martín-Nieto, J.; Cuenca, N. Tauroursodeoxycholic Acid Prevents Retinal Degeneration in Transgenic P23H Rats. Investig. Ophthalmol. Vis. Sci. 2011, 52, 4998. [Google Scholar] [CrossRef][Green Version]
  198. Olivares-González, L.; Velasco, S.; Campillo, I.; Rodrigo, R. Retinal Inflammation, Cell Death and Inherited Retinal Dystrophies. Int. J. Mol. Sci. 2021, 22, 2096. [Google Scholar] [CrossRef] [PubMed]
  199. Omura, T.; Asari, M.; Yamamoto, J.; Oka, K.; Hoshina, C.; Maseda, C.; Awaya, T.; Tasaki, Y.; Shiono, H.; Yonezawa, A.; et al. Sodium Tauroursodeoxycholate Prevents Paraquat-Induced Cell Death by Suppressing Endoplasmic Reticulum Stress Responses in Human Lung Epithelial A549 Cells. Biochem. Biophys. Res. Commun. 2013, 432, 689–694. [Google Scholar] [CrossRef] [PubMed]
  200. Zhang, T.; Baehr, W.; Fu, Y. Chemical Chaperone TUDCA Preserves Cone Photoreceptors in a Mouse Model of Leber Congenital Amaurosis. Investig. Ophthalmol. Vis. Sci. 2012, 53, 3349. [Google Scholar] [CrossRef][Green Version]
  201. Li, K.; Li, J.; Zheng, J.; Qin, S. Reactive Astrocytes in Neurodegenerative Diseases. Aging Dis. 2019, 10, 664. [Google Scholar] [CrossRef][Green Version]
  202. Eltony, S.A.; Mohaseb, H.S.; Ahmed, A.A.; Sayed, M.M. Can Metformin Modulate the Retinal Degenerative Changes in a Rat Model of Retinitis Pigmentosa? Tissue Cell 2022, 76, 101786. [Google Scholar] [CrossRef] [PubMed]
  203. Kilicarslan, I.; Zanetti, L.; Novelli, E.; Schwarzer, C.; Strettoi, E.; Koschak, A. Knockout of CaV1.3 L-Type Calcium Channels in a Mouse Model of Retinitis Pigmentosa. Sci. Rep. 2021, 11, 15146. [Google Scholar] [CrossRef]
  204. Aloe, L.; Rocco, M.L.; Bianchi, P.; Manni, L. Nerve Growth Factor: From the Early Discoveries to the Potential Clinical Use. J. Transl. Med. 2012, 10, 239. [Google Scholar] [CrossRef][Green Version]
  205. Li, B.; Ning, B.; Yang, F.; Guo, C. Nerve Growth Factor Promotes Retinal Neurovascular Unit Repair: A Review. Curr. Eye Res. 2022, 47, 1095–1105. [Google Scholar] [CrossRef]
  206. Wiatrak, B.; Kubis-Kubiak, A.; Piwowar, A.; Barg, E. PC12 Cell Line: Cell Types, Coating of Culture Vessels, Differentiation and Other Culture Conditions. Cells 2020, 9, 958. [Google Scholar] [CrossRef]
  207. Rocco, M.L.; Balzamino, B.O.; Petrocchi Passeri, P.; Micera, A.; Aloe, L. Effect of Purified Murine NGF on Isolated Photoreceptors of a Rodent Developing Retinitis Pigmentosa. PLoS ONE 2015, 10, e0124810. [Google Scholar] [CrossRef][Green Version]
  208. Rocco, M.L.; Calzà, L.; Aloe, L. NGF and Retinitis Pigmentosa: Structural and Molecular Studies. In Recent Advances in NGF and Related Molecules; Calzà, L., Aloe, L., Giardino, L., Eds.; Advances in Experimental Medicine and Biology; Springer International Publishing: Cham, Switzerland, 2021; Volume 1331, pp. 255–263. ISBN 978-3-030-74045-0. [Google Scholar]
  209. Cocchiaro, P.; Di Donato, V.; Rubbini, D.; Mastropasqua, R.; Allegretti, M.; Mantelli, F.; Aramini, A.; Brandolini, L. Intravitreal Administration of RhNGF Enhances Regenerative Processes in a Zebrafish Model of Retinal Degeneration. Front. Pharmacol. 2022, 13, 822359. [Google Scholar] [CrossRef]
  210. Bielmeier, C.B.; Schmitt, S.I.; Kleefeldt, N.; Boneva, S.K.; Schlecht, A.; Vallon, M.; Tamm, E.R.; Hillenkamp, J.; Ergün, S.; Neueder, A.; et al. Deficiency in Retinal TGFβ Signaling Aggravates Neurodegeneration by Modulating Pro-Apoptotic and MAP Kinase Pathways. Int. J. Mol. Sci. 2022, 23, 2626. [Google Scholar] [CrossRef]
  211. Eastlake, K.; Lamb, W.D.B.; Luis, J.; Khaw, P.T.; Jayaram, H.; Limb, G.A. Prospects for the Application of Müller Glia and Their Derivatives in Retinal Regenerative Therapies. Prog. Retin. Eye Res. 2021, 85, 100970. [Google Scholar] [CrossRef]
  212. Karademir, D.; Todorova, V.; Ebner, L.J.A.; Samardzija, M.; Grimm, C. Single-Cell RNA Sequencing of the Retina in a Model of Retinitis Pigmentosa Reveals Early Responses to Degeneration in Rods and Cones. BMC Biol. 2022, 20, 86. [Google Scholar] [CrossRef]
  213. Rasmussen, M.; Zhou, J.; Schwede, F.; Ekström, P. Enhanced CGMP Interactor Rap Guanine Exchange Factor 4 (EPAC2) Expression and Activity in Degenerating Photoreceptors: A Neuroprotective Response? Int. J. Mol. Sci. 2022, 23, 4619. [Google Scholar] [CrossRef]
  214. Ozawa, Y.; Toda, E.; Homma, K.; Osada, H.; Nagai, N.; Tsubota, K.; Okano, H. Effects of Epigenetic Modification of PGC-1α by a Chemical Chaperon on Mitochondria Biogenesis and Visual Function in Retinitis Pigmentosa. Cells 2022, 11, 1497. [Google Scholar] [CrossRef]
  215. Campochiaro, P.A.; Mir, T.A. The Mechanism of Cone Cell Death in Retinitis Pigmentosa. Prog. Retin. Eye Res. 2018, 62, 24–37. [Google Scholar] [CrossRef]
  216. Komeima, K.; Rogers, B.S.; Lu, L.; Campochiaro, P.A. Antioxidants Reduce Cone Cell Death in a Model of Retinitis Pigmentosa. Proc. Natl. Acad. Sci. USA 2006, 103, 11300–11305. [Google Scholar] [CrossRef] [PubMed][Green Version]
  217. Lee, S.Y.; Usui, S.; Zafar, A.; Oveson, B.C.; Jo, Y.-J.; Lu, L.; Masoudi, S.; Campochiaro, P.A. N-Acetylcysteine Promotes Long-Term Survival of Cones in a Model of Retinitis Pigmentosa. J. Cell. Physiol. 2011, 226, 1843–1849. [Google Scholar] [CrossRef] [PubMed]
  218. Yoshida, N.; Ikeda, Y.; Notomi, S.; Ishikawa, K.; Murakami, Y.; Hisatomi, T.; Enaida, H.; Ishibashi, T. Laboratory Evidence of Sustained Chronic Inflammatory Reaction in Retinitis Pigmentosa. Ophthalmology 2013, 120, e5–e12. [Google Scholar] [CrossRef] [PubMed]
  219. Johansson, I.; Monsen, V.T.; Pettersen, K.; Mildenberger, J.; Misund, K.; Kaarniranta, K.; Schønberg, S.; Bjørkøy, G. The Marine N-3 PUFA DHA Evokes Cytoprotection against Oxidative Stress and Protein Misfolding by Inducing Autophagy and NFE2L2 in Human Retinal Pigment Epithelial Cells. Autophagy 2015, 11, 1636–1651. [Google Scholar] [CrossRef] [PubMed][Green Version]
  220. Rice, D.S.; Calandria, J.M.; Gordon, W.C.; Jun, B.; Zhou, Y.; Gelfman, C.M.; Li, S.; Jin, M.; Knott, E.J.; Chang, B.; et al. Adiponectin Receptor 1 Conserves Docosahexaenoic Acid and Promotes Photoreceptor Cell Survival. Nat. Commun. 2015, 6, 6228. [Google Scholar] [CrossRef] [PubMed][Green Version]
  221. Morshedian, A.; Kaylor, J.J.; Ng, S.Y.; Tsan, A.; Frederiksen, R.; Xu, T.; Yuan, L.; Sampath, A.P.; Radu, R.A.; Fain, G.L.; et al. Light-Driven Regeneration of Cone Visual Pigments through a Mechanism Involving RGR Opsin in Müller Glial Cells. Neuron 2019, 102, 1172–1183.e5. [Google Scholar] [CrossRef] [PubMed]
  222. Ozaki, T.; Nakazawa, M.; Kudo, T.; Hirano, S.; Suzuki, K.; Ishiguro, S. Protection of Cone Photoreceptor M-Opsin Degradation with 9-Cis-β-Carotene-Rich Alga Dunaliella Bardawil in Rpe65(−/−) Mouse Retinal Explant Culture. Curr. Eye Res. 2014, 39, 1221–1231. [Google Scholar] [CrossRef] [PubMed]
  223. Pawlyk, B.S.; Li, T.; Scimeca, M.S.; Sandberg, M.A.; Berson, E.L. Absence of Photoreceptor Rescue with D-Cis-Diltiazem in the Rd Mouse. Investig. Ophthalmol. Vis. Sci. 2002, 43, 1912–1915. [Google Scholar]
  224. Yang, J.; Weimer, R.M.; Kallop, D.; Olsen, O.; Wu, Z.; Renier, N.; Uryu, K.; Tessier-Lavigne, M. Regulation of Axon Degeneration after Injury and in Development by the Endogenous Calpain Inhibitor Calpastatin. Neuron 2013, 80, 1175–1189. [Google Scholar] [CrossRef][Green Version]
  225. Yamamoto, S.; Sugawara, T.; Murakami, A.; Nakazawa, M.; Nao-I, N.; Machida, S.; Wada, Y.; Mashima, Y.; Myake, Y. Topical Isopropyl Unoprostone for Retinitis Pigmentosa: Microperimetric Results of the Phase 2 Clinical Study. Ophthalmol. Ther. 2012, 1, 5. [Google Scholar] [CrossRef][Green Version]
  226. Sahaboglu, A.; Vidal-Gil, L.; Sancho-Pelluz, J. Release of Retinal Extracellular Vesicles in a Model of Retinitis Pigmentosa. In Retinal Degenerative Diseases; Bowes Rickman, C., Grimm, C., Anderson, R.E., Ash, J.D., LaVail, M.M., Hollyfield, J.G., Eds.; Advances in Experimental Medicine and Biology; Springer International Publishing: Cham, Switzerland, 2019; Volume 1185, pp. 431–436. ISBN 978-3-030-27377-4. [Google Scholar]
  227. Knickelbein, J.E.; Liu, B.; Arakelyan, A.; Zicari, S.; Hannes, S.; Chen, P.; Li, Z.; Grivel, J.-C.; Chaigne-Delalande, B.; Sen, H.N.; et al. Modulation of Immune Responses by Extracellular Vesicles From Retinal Pigment Epithelium. Investig. Ophthalmol. Vis. Sci. 2016, 57, 4101. [Google Scholar] [CrossRef][Green Version]
  228. Ma, M.; Li, B.; Zhang, M.; Zhou, L.; Yang, F.; Ma, F.; Shao, H.; Li, Q.; Li, X.; Zhang, X. Therapeutic Effects of Mesenchymal Stem Cell-Derived Exosomes on Retinal Detachment. Exp. Eye Res. 2020, 191, 107899. [Google Scholar] [CrossRef]
  229. Liu, Y.; Zhou, T.; Yang, Z.; Sun, X.; Huang, Z.; Deng, X.; He, C.; Liu, X. Bone Marrow Mesenchymal Stem Cells-Derived Exosomes Attenuate Neuroinflammation and Promote Survival of Photoreceptor in Retinitis Pigmentosa. Investig. Ophthalmol. Vis. Sci. 2019, 60, 3108. [Google Scholar]
  230. Odagiu, L.; May, J.; Boulet, S.; Baldwin, T.A.; Labrecque, N. Role of the Orphan Nuclear Receptor NR4A Family in T-Cell Biology. Front. Endocrinol. 2020, 11, 624122. [Google Scholar] [CrossRef] [PubMed]
  231. Wang, Y.; Zhang, Q.; Yang, G.; Wei, Y.; Li, M.; Du, E.; Li, H.; Song, Z.; Tao, Y. RPE-Derived Exosomes Rescue the Photoreceptors during Retina Degeneration: An Intraocular Approach to Deliver Exosomes into the Subretinal Space. Drug Deliv. 2021, 28, 218–228. [Google Scholar] [CrossRef] [PubMed]
  232. Deng, C.-L.; Hu, C.-B.; Ling, S.-T.; Zhao, N.; Bao, L.-H.; Zhou, F.; Xiong, Y.-C.; Chen, T.; Sui, B.-D.; Yu, X.-R.; et al. Photoreceptor Protection by Mesenchymal Stem Cell Transplantation Identifies Exosomal MiR-21 as a Therapeutic for Retinal Degeneration. Cell Death Differ. 2021, 28, 1041–1061. [Google Scholar] [CrossRef] [PubMed]
  233. Jenike, A.E.; Halushka, M.K. MiR-21: A Non-specific Biomarker of All Maladies. Biomark. Res. 2021, 9, 18. [Google Scholar] [CrossRef]
  234. Bian, B.; Zhao, C.; He, X.; Gong, Y.; Ren, C.; Ge, L.; Zeng, Y.; Li, Q.; Chen, M.; Weng, C.; et al. Exosomes Derived from Neural Progenitor Cells Preserve Photoreceptors during Retinal Degeneration by Inactivating Microglia. J. Extracell. Vesicles 2020, 9, 1748931. [Google Scholar] [CrossRef][Green Version]
  235. Zhang, Z.; Mugisha, A.; Fransisca, S.; Liu, Q.; Xie, P.; Hu, Z. Emerging Role of Exosomes in Retinal Diseases. Front. Cell Dev. Biol. 2021, 9, 643680. [Google Scholar] [CrossRef]
  236. Elliott, R.O.; He, M. Unlocking the Power of Exosomes for Crossing Biological Barriers in Drug Delivery. Pharmaceutics 2021, 13, 122. [Google Scholar] [CrossRef]
  237. Liang, Y.; Duan, L.; Lu, J.; Xia, J. Engineering Exosomes for Targeted Drug Delivery. Theranostics 2021, 11, 3183–3195. [Google Scholar] [CrossRef]
  238. Hung, M.E.; Leonard, J.N. Stabilization of Exosome-Targeting Peptides via Engineered Glycosylation. J. Biol. Chem. 2015, 290, 8166–8172. [Google Scholar] [CrossRef][Green Version]
  239. Boukouris, S.; Mathivanan, S. Exosomes in Bodily Fluids Are a Highly Stable Resource of Disease Biomarkers. Proteom. Clin. Appl. 2015, 9, 358–367. [Google Scholar] [CrossRef][Green Version]
  240. Wassmer, S.J.; Carvalho, L.S.; György, B.; Vandenberghe, L.H.; Maguire, C.A. Exosome-Associated AAV2 Vector Mediates Robust Gene Delivery into the Murine Retina upon Intravitreal Injection. Sci. Rep. 2017, 7, 45329. [Google Scholar] [CrossRef] [PubMed][Green Version]
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.
This entry is offline, you can click here to edit this entry!
Feedback