Submitted Successfully!
To reward your contribution, here is a gift for you: A free trial for our video production service.
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Version Summary Created by Modification Content Size Created at Operation
1
Solmaz Abdolrahimzadeh
 -- 2781 2024-02-28 10:29:14 |
2 layout
Jessie Wu
 + 7 word(s) 2788 2024-02-29 04:16:49 |

Video Upload Options

Do you have a full video?
Send video materials Upload full video

Confirm

Are you sure to Delete?
Yes No
Cite
If you have any further questions, please contact Encyclopedia Editorial Office.
Ruggeri, F.; Ciancimino, C.; Guillot, A.; Fumi, D.; Tizio, F.D.; Fragiotta, S.; Abdolrahimzadeh, S. Posterior Polar Annular Choroidal Dystrophy. Encyclopedia. Available online: https://encyclopedia.pub/entry/55644 (accessed on 13 June 2024).
Ruggeri F, Ciancimino C, Guillot A, Fumi D, Tizio FD, Fragiotta S, et al. Posterior Polar Annular Choroidal Dystrophy. Encyclopedia. Available at: https://encyclopedia.pub/entry/55644. Accessed June 13, 2024.
Ruggeri, Francesco, Chiara Ciancimino, Antonio Guillot, Daniele Fumi, Federico Di Tizio, Serena Fragiotta, Solmaz Abdolrahimzadeh. "Posterior Polar Annular Choroidal Dystrophy" Encyclopedia, https://encyclopedia.pub/entry/55644 (accessed June 13, 2024).
Ruggeri, F., Ciancimino, C., Guillot, A., Fumi, D., Tizio, F.D., Fragiotta, S., & Abdolrahimzadeh, S. (2024, February 28). Posterior Polar Annular Choroidal Dystrophy. In Encyclopedia. https://encyclopedia.pub/entry/55644
Ruggeri, Francesco, et al. "Posterior Polar Annular Choroidal Dystrophy." Encyclopedia. Web. 28 February, 2024.
Posterior Polar Annular Choroidal Dystrophy
Edit
This entry is adapted from the peer-reviewed paper 10.3390/cimb46020089

Posterior polar annular choroidal dystrophy (PPACD) is a rare ocular disorder and presents as symmetric degeneration of the retinal pigment epithelium (RPE) and the underlying choriocapillaris, encircling the retinal vascular arcades and optic disc. This condition distinctively preserves the foveal region, optic disc, and the outermost regions of the retina. Despite its distinct clinical presentation, due to the infrequency of its occurrence and the limited number of reported cases, the pathophysiology, and the genetic foundations of PPACD are still largely uncharted.

posterior polar annular choroidal dystrophy multimodal imaging spectral domain optic coherence tomography

1. Posterior Polar Annular Choroidal Dystrophy Diagnostic Approaches

1.1. Fundus Examination

Since its first documentation by Yannuzzi and colleagues in 2010 the funduscopic appearance presented peculiar morphological phenotypical characteristics [1]. Characteristically, peripapillary chorioretinal atrophy spreads toward the temporal vascular arcades, configuring an annular pattern with foveal sparing. Lesions are often asymmetric between eyes, with one eye that is more severely involved. In one case, Lenis and colleagues reported that a symmetric atrophy was noted in both eyes [2]. Although discrete pigment aggregations can be observed within the atrophic regions, the peripheral retina is devoid of bone spicule-like pigment alterations and arteriolar narrowing, distinguishing this entity from other inherited retinal dystrophies [2][3][4][5][6].

1.2. Fundus Autofluorescence

FAF has emerged as a pivotal noninvasive technique for various retinal disorders, especially in the spectrum of retinal and choroidal dystrophies. FAF imaging is based on the caption of light emitted from lipofuscin in the RPE, where an increased autofluorescence typically signifies an accumulation of fluorophores within the RPE [7].
In PPACD, short wavelength FAF shows an annular pattern of hypoautofluorescence in a peripapillary distribution, extending concentrically towards the retinal vascular arcades corresponding to the chorioretinal atrophy. A perifoveal hyperautofluorescent border can be frequently observed and demarcates the transition from healthy to atrophic retinal tissue [2][3][4][5][8].

1.3. Fluorescein Angiography

FA typically shows a window defect in the atrophic area with visualization of the underlying choroidal vasculature attributable to choriocapillaris and RPE loss. Moreover, a pattern of concentric staining in the late frames around the optic disk and central macula can be appreciated [2][5][6][8]. Tabbaa and colleagues demonstrated areas of late leakage surrounding the fovea in one case with PPHCD [8].

1.4. Optical Coherence Tomography

SD-OCT typically reveals the reduced thickness of the outer retina and the choriocapillaris colocalizing with the regions exhibiting the atrophic changes on clinical examination, while the remaining retina appears intact. Additionally, disturbances in the organization of the outer retina and alterations in the ellipsoid zone have been observed [5]. Furthermore, the concomitance of intraretinal cystic changes was noted in two distinct cases, with parafoveal localization in one case [8] and bilateral central cystoid changes in the other case [5].
Swept-source optical coherence tomography (SS-OCT) represents an enhancement in imaging capabilities, offering superior resolution and deeper tissue penetration [9][10]. SS-OCT confirmed the presence of retinal thinning, rarefaction of the ellipsoid band, and RPE with choriocapillaris attenuation [3][4][6]. Sone et al. [4] also noticed a dilation of the Sattler and Haller’s choroidal vascular layers. The enface maps segmented on RPE further demonstrated the dilation of these vascular layers. However, Narayan [6] reported a reduction of choroidal thickness in the areas involved with a reduced Sattler’s layer.
Of note, despite OCT B scans enabling high-resolution cross-sectional visualization of the retina, it is crucial to recognize the distribution of the lesions in PPACD. Indeed, the predilection of PPACD for the mid- and peripheral retina [3][4][5][6][8][11] necessitates expanding the scan area to capture the pathological features. In this regard, wide-field OCT may facilitate a more precise monitoring of disease progression. By documenting changes in retinal thickness and structure in a broader area, the peripheral spread of the dystrophy can be tracked with greater accuracy. This information is vital for prognostic assessment and for tailoring, monitoring, and management strategies to the individual patient’s needs [12].

1.5. Optical Coherence Tomography Angiography

OCTA showed a preservation of the central superficial vascular plexus. Conversely, a notable reduction in flow signal was noted in the deep capillary plexus, accompanied by a significant rarefaction of the choriocapillaris corresponding to the affected areas [5][6]. The reduction of vascular flow on OCTA was hypothesized to be secondary to outer retina atrophy, thus confirming that the disease can be in the dystrophic spectrum [6].

1.6. Perimetric Testing

Perimetric testing performed in cases of PPACD [4][8] showed superior arcuate scotomas in both eyes, aligning with the atrophic regions observable upon funduscopic examination. In the two cases reported by Lenis and colleagues, the authors reported enlarged blind spots in perimetric testing correlating with the pattern of peripapillary atrophy [2]. Others [3][6] demonstrated generalized depressed points, predominantly in the pericentral area [3].

1.7. Full-Field Electroretinography

Full-field ERG in PPACD typically shows predominately diffused depressed responses, not solely restricted to the atrophic regions [6][8][13]. However, there is a diminished response in both scotopic and photopic a-wave and b-wave amplitudes, alongside a decrease in the 30 Hz flicker response, and oscillatory potentials with a prolongation of implicit time [3][6]. In the full-field ERG analysis, a mild decrease in the a-wave amplitudes under scotopic conditions and combined rod–cone responses were observed for both eyes. The cone and 30 Hz flicker responses appeared within the normal range but were slightly reduced [4]. In a documented case by Del Valle et al., full-field ERG demonstrated diminished cone function while rod function remained within normal limits, suggesting widespread cone dysfunction [5]. This finding stands in contrast to other observed results.

1.8. Laser Speckle Flowgraphy

Laser speckle flowgraphy (LSFG) is a dye-free imaging mode that utilizes the statistical analysis of laser speckle patterns to evaluate ocular blood flow. This technique has been demonstrated to be useful in assessing circulatory dynamics within the retina, optic nerve head (ONH), and choroidal vessels [14]. LSFG was conducted in only one case with PPACD revealing a cold spectrum in the color range of both eyes [4]. A summary of PPACD appearance with different imaging modalities can se seen in Table 1.
Table 1. Summary of posterior polar annular choroidal dystrophy (PPACD) appearance with different imaging modalities.
Imaging Modality PPACD Appearance
Fundus Examination Peripapillary chorioretinal atrophy reaches out towards the temporal vascular arcade, creating an annular pattern while leaving the foveal area unaffected asymmetricity is often found [2][3][4][5][6][8].
FAF Annular pattern of hypoautofluorescence in a peripapillary distribution, extending in a concentric pattern to the temporal arcades that corresponds to the area of atrophy of the chorioretina. A perifoveal hyperautofluorescent border frequently demarcates the transition from healthy to atrophic retinal tissue [2][3][4][5][8].
FA Window defect with visualization of the underlying choroidal vasculature attributable to an absence of perfusion in the retinal and choroidal vessels, along with staining in the late frames in a concentric configuration surrounding the optic disc and central macula. Areas of late leakage surrounding the fovea in one case [8].
SD-OCT Thinning of the outer retina and choriocapillaris in regions exhibiting atrophic changes. Additionally, disturbances in the organization of the outer retinal structures and alterations in the EZ have been observed [8]. Involvement of the parafovea with parafoveal cystic intraretinal fluid was reported in one case [8]. Only one case [5] presented cystoid macular edema and outer retinal atrophy leaving the subfoveal area unaffected.
SS-OCT Physiological foveal and subfoveal choroid, with marked thinning of the retina with complete disorganization of retinal layers in the atrophic chorioretinal area. In the atrophic regions, there is typically a notable decrease in the thickness of the choroid, characterized by the absence of Sattler’s layer and diminished choroidal vascularity [3][4][6].
OCTA In the context of retinal atrophy, imaging often reveals the preservation of normal vascularization within the foveal and subfoveal choroidal regions. Conversely, there is a notable diminution in the depth of the capillary plexus, along with an evident depletion of the choriocapillaris corresponding to the atrophic zones observed in both eyes [5][6].
Perimetric Testing Two cases [4][8] showed superior arcuate scotomas in botheyes. In the two cases reported by Lenis and colleagues, the authors reported enlarged blind spots in perimetric testing correlating with the pattern of peripapillary atrophy [2]. In the case reported by Narayanan and colleagues in 2019, perimetric testing demonstrated generalized depressed points, predominantly in the pericentral area [3].
ERG Predominately depressed cone responses with normal rod responses, and not only in the atrophy region. In the case reported by Narayanan and colleagues in 2019, each eye exhibited a diminished response in both scotopic and photopic a-wave and b-wave amplitudes, alongside a decrease in the 30 Hz flicker response and oscillatory potentials, coupled with a prolongation of implicit times [3]. Sone and colleagues reported a case of mild reduction of a-wave amplitudes in scotopic and combined rod–cone responses in both eyes.
LSFG LSFG was conducted in only one case and it showed diminished warmth in the coloration at the posterior pole in both eyes [4].
FAF: Fundus Autofluorescence; FA: Fluorescein Angiography; SDOCT: Spectral-domain Optical Coherence Tomography; EZ: Ellipsoid Zone; SSOCT: Swept-source Optical Coherence Tomography; OCTA: Optical Coherence Tomography Angiography; ERG: Full-field Electroretinogram; LSFG: Laser speckle flowgraphy.

2. Genetic Basis of Posterior Polar Annular Choroidal Dystrophy

The scarcity of literature addressing the casuistry associated with PPACD is evident in the limited utilization of genetic screenings in affected individuals. Specifically, there exist only two case reports wherein potential genetic correlations were systematically assessed, focusing on distinct genetic loci. In the case documented by Lenis et al. [2], no substantial mutations were documented after testing genes such as ABCA4, BEST1, PRPH2, CDH3, EFEMP1, ELOVL4, IMPG1, IMPG2, PROM1, RDS, and TIMP3. Furthermore, no analogous clinical or semiotic aberrations were observed in first-degree relatives. In a second case suffering from PPHCD [8], a standardized SPARK Inherited Retinal Dystrophy (IRD) panel was performed testing several mutations of indeterminate significance across multiple genes, including CCD2D2A, CEP78, NR2E3, PCARE, PEX14, and RPGRIP1. Unfortunately, the utility of identifying these mutations is constrained by various factors, with the primary challenge being the unique nature of the sample in which their presence is evident. The establishment of clear connections between specific gene mutations (genotype) and disease characteristics (phenotype) is thus, hindered. Additionally, it is crucial to recognize that many of the implicated genes lack a fully defined role within the retina, leading to significant gaps in certain phenotype–genotype correlations.
In this context, Next-generation Sequencing (NGS) could be pivotal, offering detailed insights into the genetic landscape of PPACD by identifying both prevalent and rare variants that might be implicated in its pathogenesis [15].
Nevertheless, NGS presents challenges, including the complex analysis of vast genomic data sets and distinguishing between pathogenic mutations and benign variants. The integration of NGS into PPACD research holds promise for uncovering new genetic targets and enhancing personalized medicine approaches. However, this requires the collaborative effort of experts in genomics, bioinformatics, and ophthalmology to fully interpret the intricate data NGS provides, all within the clinical context of PPACD [15].
Notably, a substantial proportion of the mutations under scrutiny are associated with cone–rod dystrophy, implicating a common pathogenesis that specifically affects photoreceptors [8]. The potential genetic involvement in PPACD is encouraged by characteristic features, such as night blindness, ERG alterations, and visual field defects.
Sharon and colleagues indicate that the RPE allocates over 9.5% of its transcripts to the synthesis of proteins involved in this degradation process, a stark contrast to the neural retina, which dedicates less than 3% [16]. This disparity underscores the specialized function of the RPE in maintaining photoreceptor health and potentially implicates the degradation pathway in the pathology of retinal diseases like PPACD [16]. Given the essential functions of the RPE in photoreceptor maintenance and the nascent understanding of its genetic landscape, it becomes increasingly important to explore how aberrations in these genes might contribute to retinal dystrophies. In particular, the identification of pathologic mutations within RPE-related genes may offer valuable insights into the molecular underpinnings of PPACD. This understanding is crucial not only for the diagnosis and prognosis of the disease but also for the development of targeted therapies that address the underlying genetic defects [16].
In this section, the genes potentially involved in PPACD and their role in maintaining retinal homeostasis are discussed.
A case report found a PPHCD patient positive for a partial NR2E3 deletion demonstrating a role of this gene in the phenotypic manifestations of the pathology [8].
The nuclear receptor NR2E3, commonly known as the photoreceptor-specific nuclear receptor (PNR), is a transcriptional regulator localized to photoreceptors in both the developing and adult retina and is part of the extensive nuclear hormone receptor superfamily [17][18]. Conditions associated with mutations in NR2E3 are marked by a reduced population of rod photoreceptors alongside an increase in cells resembling short-wavelength sensitive cones [18]. Researchers have discovered thirty-two distinct mutations in the NR2E3 gene. Clinically, mutations in the NR2E3 gene manifest in several IRDs sharing common symptoms such as early-onset nyctalopia and minimal rod cell functionality, phenotypic characteristics typically found in PPACD [17][19].
NR2E3 is part of the nuclear receptor family, comprising 48 members, including endocrine and orphan receptors [20]. During the embryonic stages, both rod and cone cells originate from a shared precursor specific to photoreceptors [20][21]. The NR2E3 gene plays a pivotal role in guiding the differentiation toward the rod cells rather than the cones. Investigations involving both animal models and humans with NR2E3 mutations indicate that this gene has a dual function in photoreceptor differentiation: it inhibits the expression of genes associated with cones, e.g., OPNSW1 (encoding blue opsin), GNAT2, and the cone transducin subunits, while simultaneously facilitating the activation of genes specific to rods, including GNB1 (the rod transducin β subunit) and rhodopsin [20].
In the genetic analysis performed in the case of PPHCD, different variants of uncertain significance emerged, including CC2D2A, CEP78, NR2E3, PCARE, PEX14, and RPGRIP1 [8].
PCARE is postulated to be critical in the early stages of outer segment (OS) disk formation, orchestrating the relocation of actin-associated elements to the photoreceptor OS foundation. Rod photoreceptors undergo a daily renewal process where approximately 10% of their opsin-rich disks at the apical tip of the OS are shed and subsequently engulfed by neighboring RPE cells. The genesis of new photoreceptor disks commences at the site where the connecting cilium (CC) adjoins the OS base, marked by an outpouching of the ciliary plasma membrane. The protein PCARE is known to predominantly interact with WASF3, which influences the actin scaffolding within the cell by stimulating the ARP2/3 complex. This stimulation is a precursor to the formation of a branched network of F-actin from G-actin, an essential structure for the ciliary membrane to protrude, facilitating the enlargement of the ciliary apex that drives disk morphogenesis. Clinically, patients often exhibit initial deterioration in the cone photoreceptor system, evident through macular abnormalities and annular scotomas during visual field evaluation [22].
RPGRIP1 encodes the retinitis pigmentosa (RP) GTPase regulator interaction protein. It is situated on chromosome 14 (14q11.2) and spans 63 kb, comprising 24 exons that translate into a protein consisting of 1286 amino acids [23][24]. The gene RPGRIP1 synthesizes the protein known as the RP GTPase regulator interaction protein plays a fundamental role in the functions of the retina. Its activity is aligned with that of its molecular associate, the RPGR, at the OS of photoreceptors in humans. RPGRIP1 plays a vital role in protein transport regulation from the inner to OS of these cells [23][24][25]. Experimental models in mice have illustrated the essential role of RPGRIP1 in the development of photoreceptor disk morphology; photoreceptor degeneration occurs despite the normal initial formation of rods and cones [23][24]. The Human Gene Mutation Database (HGMD) documents various pathogenic mutations in RPGRIP1, such as missense, splicing, deletion, duplication, and frameshift variations. Moreover, infrequent structural variations and complex mutations, including noncoding mutations like a homozygous deletion within exon 17 of RPGRIP1, have been identified. These findings suggest that complex and noncoding mutations could substantially contribute to the overall mutational landscape of the gene [23][24][26]. A summary of retinal genes and their function can be found in Table 2.
Table 2. Summary of retinal genes: functional roles and chromosomal locations.
Gene Biological Role Associated Retinal Processes Chromosomal Location
ABCA4 ATP-binding cassette transporter [27][28][29][30][31][32] Protein involved in the visual cycle of photoreceptors [27][28][29][30][31][32] 1p22.1 [27][28][31]
BEST1 Integral membrane protein [33] Involved in ion transport across RPE [33] 11q13 [33]
PRPH2 Cell-surface protein [34] Plays a role in the visual phototransduction process and in the structural integrity of photoreceptor outer segments [34] 6p21.1 [34]
CDH3 Cell–cell adhesion glycoprotein [35][36] Cadherin-related protein, may play a role in cell adhesion [35][36] 16q22.1 [35][36]
EFEMP1 Extracellular matrix protein [37] Associated with the extracellular matrix and may influence eye development [37] 2p16.1 [37]
ELOVL4 Membrane-bound protein [38][39] Involved in the elongation of very long-chain fatty acids [38][39][40] 6q14.1 [38][39][40]
IMPG1 Matrix proteoglycan [41][42][43] Plays a role in the homeostasis and function of the retinal pigment epithelium [41][42][43] 6q14.2 [41][42][43]
IMPG2 Matrix proteoglycan [44][45][46] Involved in the structural integrity of the photoreceptor outer segment [44][45][46] 3q12.3 [44][45][46]
PROM1 Transmembrane protein [47][48] Involved in photoreceptor disk morphogenesis [47][48] 4p15.32 [47][48]
TIMP3 Metallopeptidase inhibitor [49] Involved in ocular development [49] 22q12.3 [49]
CCD2D2A Binding domain protein [8] Uncertain significance, possibly related to cilia structure and function [8] 4q21.1 [8]
CEP78 Centrosomal protein [50] May be involved in ciliary functions [50] 9q21.13 [50]
NR2E3 Nuclear receptor [8][20][21][51] Key transcription factor for photoreceptor development [8][20][21][51] 15q23 [20][21]
PCARE Ciliary and actin-associated protein [8][22][52] Probably associated with the primary cilium of the outer segment [8][22][52] 2p23.2 [52]

References

  1. Yannuzzi, L.A.; Bailey Freund, K.; Sarraf, D.; Mieler, W.F. The Retinal Atlas, 2nd ed.; Elsevier Health Sciences: Amsterdam, The Netherlands, 2010.
  2. Lenis, T.L.; Klufas, M.A.; Randhawa, S.; Sharma, M.; Sarraf, D. Posterior Polar Annular Choroidal Dystrophy: A Case Series. Retin. Cases Brief Rep. 2017, 11 (Suppl. S1), S24–S27.
  3. Gala, J.M.; Narayanan, R. Posterior Polar Annular Choroidal Dystrophy. BMJ Case Rep. 2019, 12, e230495.
  4. Sone, R.; Noda, K.; Hirooka, K.; Saito, M.; Ishida, S. Insidious Progression of Atrophic Lesions in a Case of Posterior Polar Annular Choroidal Dystrophy. Am. J. Ophthalmol. Case Rep. 2022, 28, 101708.
  5. Del Valle-Nava, F.; Sánchez-Ramos, J.; Hernández-Vázquez, A.; Gonzalez-Saldivar, G.; Ramirez-Estudillo, A. Posterior Polar Annular Choroidal Dystrophy Association with Cystoid Macular Edema. Clin. Case Rep. 2019, 7, 389–390.
  6. Narayanan, R. Posterior Polar Annular and Hemispheric Choroidal and Retinal Dystrophy: Optical Coherence Tomographic Angiography Description of a Rare Case. Indian J. Ophthalmol. 2018, 66, 1874–1876.
  7. Tsang, S.H.; Sharma, T. Fundus Autofluorescence. Adv. Exp. Med. Biol. 2018, 1085, 15–16.
  8. Tabbaa, T.; Daroszewski, D.; Sobol, W. Posterior Polar Hemispheric Choroidal Dystrophy: Case Report and Presentation of Genetic Screening. J. VitreoRetinal Dis. 2022, 6, 485–490.
  9. Drexler, W.; Liu, M.; Kumar, A.; Kamali, T.; Unterhuber, A.; Leitgeb, R.A. Optical Coherence Tomography Today: Speed, Contrast, and Multimodality. J. Biomed. Opt. 2014, 19, 071412.
  10. Huang, Y.; Lan, J.; Zang, X.; Huan, Y.; Xie, L. Optical Coherence Tomography-Guided Intracameral Air Injection for Treatment of Extensive Descemet’s Membrane Detachment. Br. J. Ophthalmol. 2012, 96, 1441–1443.
  11. Forte, R.; Aptel, F.; Feldmann, A.; Chiquet, C. Multimodal Imaging of Posterior Polar Annular Choroidal Dystrophy. Retin. Cases Brief Rep. 2018, 12, 29–32.
  12. Gregori, N.Z.; Lam, B.L.; Gregori, G.; Ranganathan, S.; Stone, E.M.; Morante, A.; Abukhalil, F.; Aroucha, P.R. Wide-Field Spectral-Domain Optical Coherence Tomography in Patients and Carriers of X-Linked Retinoschisis. Ophthalmology 2013, 120, 169–174.
  13. Bommakanti, N.; Besirli, C.G.; Zhao, P.Y. Retinal Neovascularization in Posterior Polar Annular Choroidal Dystrophy. JAMA Ophthalmol. 2023, 141, 102–104.
  14. Lu, Y.; Zhou, H.; Zhou, X.; Chen, Y.; Wang, R.K. Correlation Between Laser Speckle Flowgraphy and OCT-Derived Retinal and Choroidal Metrics in Healthy Human Eye. Transl. Vis. Sci. Technol. 2022, 11, 15.
  15. Satam, H.; Joshi, K.; Mangrolia, U.; Waghoo, S.; Zaidi, G.; Rawool, S.; Thakare, R.P.; Banday, S.; Mishra, A.K.; Das, G.; et al. Next-Generation Sequencing Technology: Current Trends and Advancements. Biology 2023, 12, 997.
  16. Sharon, D.; Blackshaw, S.; Cepko, C.L.; Dryja, T.P. Profile of the Genes Expressed in the Human Peripheral Retina, Macula, and Retinal Pigment Epithelium Determined through Serial Analysis of Gene Expression (SAGE). Proc. Natl. Acad. Sci. USA 2002, 99, 315–320.
  17. Schorderet, D.F.; Escher, P. NR2E3 Mutations in Enhanced S-Cone Sensitivity Syndrome (ESCS), Goldmann-Favre Syndrome (GFS), Clumped Pigmentary Retinal Degeneration (CPRD), and Retinitis Pigmentosa (RP). Hum. Mutat. 2009, 30, 1475–1485.
  18. Hamel, C. Retinitis Pigmentosa. Orphanet J. Rare Dis. 2006, 1, 40.
  19. Connor, B.; Titialii-Torres, K.; Rockenhaus, A.E.; Passamonte, S.; Morris, A.C.; Lee, Y.-S. Biliverdin Regulates NR2E3 and Zebrafish Retinal Photoreceptor Development. Sci. Rep. 2022, 12, 7310.
  20. Toms, M.; Ward, N.; Moosajee, M. Nuclear Receptor Subfamily 2 Group E Member 3 (NR2E3): Role in Retinal Development and Disease. Genes 2023, 14, 1325.
  21. Haider, N.B.; Mollema, N.; Gaule, M.; Yuan, Y.; Sachs, A.J.; Nystuen, A.M.; Naggert, J.K.; Nishina, P.M. Nr2e3-Directed Transcriptional Regulation of Genes Involved in Photoreceptor Development and Cell-Type Specific Phototransduction. Exp. Eye Res. 2009, 89, 365–372.
  22. Zufiaurre-Seijo, M.; García-Arumí, J.; Duarri, A. Clinical and Molecular Aspects of C2orf71/PCARE in Retinal Diseases. Int. J. Mol. Sci. 2023, 24, 10670.
  23. Koenekoop, R.K. RPGRIP1 Is Mutated in Leber Congenital Amaurosis: A Mini-Review. Ophthalmic Genet. 2005, 26, 175–179.
  24. Zou, G.; Zhang, T.; Cheng, X.; Igelman, A.D.; Wang, J.; Qian, X.; Fu, S.; Wang, K.; Koenekoop, R.K.; Fishman, G.A.; et al. Noncoding Mutation in RPGRIP1 Contributes to Inherited Retinal Degenerations. Mol. Vis. 2021, 27, 95–106.
  25. Roepman, R.; Bernoud-Hubac, N.; Schick, D.E.; Maugeri, A.; Berger, W.; Ropers, H.H.; Cremers, F.P.; Ferreira, P.A. The Retinitis Pigmentosa GTPase Regulator (RPGR) Interacts with Novel Transport-like Proteins in the Outer Segments of Rod Photoreceptors. Hum. Mol. Genet. 2000, 9, 2095–2105.
  26. Suzuki, T.; Fujimaki, T.; Yanagawa, A.; Arai, E.; Fujiki, K.; Wada, Y.; Murakami, A. A Novel Exon 17 Deletion Mutation of RPGRIP1 Gene in Two Siblings with Leber Congenital Amaurosis. Jpn. J. Ophthalmol. 2014, 58, 528–535.
  27. Cevik, S.; Wangtiraumnuay, N.; Van Schelvergem, K.; Tsukikawa, M.; Capasso, J.; Biswas, S.B.; Bodt, B.; Levin, A.V.; Biswas-Fiss, E. Protein Modeling and in Silico Analysis to Assess Pathogenicity of ABCA4 Variants in Patients with Inherited Retinal Disease. Mol. Vis. 2023, 29, 217–233.
  28. Cremers, F.P.M.; Lee, W.; Collin, R.W.J.; Allikmets, R. Clinical Spectrum, Genetic Complexity and Therapeutic Approaches for Retinal Disease Caused by ABCA4 Mutations. Prog. Retin. Eye Res. 2020, 79, 100861.
  29. De Angeli, P.; Flores-Tufiño, A.; Stingl, K.; Kühlewein, L.; Roschi, E.; Wissinger, B.; Kohl, S. Splicing Defects and CRISPR-Cas9 Correction in Isogenic Homozygous Photoreceptor Precursors Harboring Clustered Deep-Intronic ABCA4 Variants. Mol. Ther. Nucleic Acids 2024, 35, 102113.
  30. Fujinami, K.; Zernant, J.; Chana, R.K.; Wright, G.A.; Tsunoda, K.; Ozawa, Y.; Tsubota, K.; Webster, A.R.; Moore, A.T.; Allikmets, R.; et al. ABCA4 Gene Screening by Next-Generation Sequencing in a British Cohort. Investig. Ophthalmol. Vis. Sci. 2013, 54, 6662–6674.
  31. Michaelides, M.; Chen, L.L.; Brantley, M.A.; Andorf, J.L.; Isaak, E.M.; Jenkins, S.A.; Holder, G.E.; Bird, A.C.; Stone, E.M.; Webster, A.R. ABCA4 Mutations and Discordant ABCA4 Alleles in Patients and Siblings with Bull’s-Eye Maculopathy. Br. J. Ophthalmol. 2007, 91, 1650–1655.
  32. Molday, R.S. Insights into the Molecular Properties of ABCA4 and Its Role in the Visual Cycle and Stargardt Disease. Prog. Mol. Biol. Transl. Sci. 2015, 134, 415–431.
  33. Singuri, S.; DeBenedictis, M.J.; Traboulsi, E.I.; Yuan, A.; Schur, R.M. BEST1 Variant Associated with an Atypical Macular and Peripheral Retinal Phenotype. Retin. Cases Brief Rep. 2023.
  34. Mulders, T.; van der Zanden, L.; Klevering, B.J.; Hoyng, C.; Theelen, T. Structure-Function Correlation of Retinal Photoreceptors in PRPH2-Associated Central Areolar Choroidal Dystrophy Patients Assessed by High-Resolution Scanning Laser Imaging and Microperimetry. Acta Ophthalmol. 2023. Early View.
  35. Yusuf, I.H.; Garrett, A.M.; MacLaren, R.E.; Charbel Issa, P. Retinal Cadherins and the Retinal Cadherinopathies: Current Concepts and Future Directions. Prog. Retin. Eye Res. 2022, 90, 101038.
  36. Al Zubi, K.; Mwafi, N.; Alrawashdeh, H.M.; Al Sarireh, F.; Somkuwar, A.; Abdulmannan, D.M. The First Reported Case of CDH3-Related Hypotrichosis with Juvenile Macular Dystrophy from Jordan: A Case Report. Ophthalmic Genet. 2022, 43, 420–424.
  37. Lin, S.; Vermeirsch, S.; Pontikos, N.; Martin-Gutierrez, M.P.; Varela, M.D.; Malka, S.; Schiff, E.; Knight, H.; Wright, G.; Jurkute, N.; et al. Spectrum of Genetic Variants in the Commonest Genes Causing Inherited Retinal Disease in a Large Molecularly Characterised UK Cohort. Ophthalmol. Retina 2024, in press.
  38. Nwagbo, U.; Bernstein, P.S. Understanding the Roles of Very-Long-Chain Polyunsaturated Fatty Acids (VLC-PUFAs) in Eye Health. Nutrients 2023, 15, 3096.
  39. Alabdulrazzaq, F.; Alanzi, T.; Al-Balool, H.H.; Gardham, A.; Wakeling, E.; Leitch, H.G.; AlSayed, M.; Abdulrahim, M.; Aladwani, A.; Romito, A.; et al. Expanding the Allelic Spectrum of ELOVL4-Related Autosomal Recessive Neuro-Ichthyosis. Mol. Genet. Genom. Med. 2023, 11, e2256.
  40. Gyening, Y.K.; Boris, K.; Cyril, M.; Brush, R.S.; Nassogne, M.-C.; Agbaga, M.-P. A Novel ELOVL4 Variant, L168S, Causes Early Childhood-Onset Spinocerebellar Ataxia-34 and Retinal Dysfunction: A Case Report. Acta Neuropathol. Commun. 2023, 11, 131.
  41. Olivier, G.; Brabet, P.; Pirot, N.; Broyon, M.; Guillou, L.; Cazevieille, C.; Sar, C.; Quiles, M.; Sarzi, E.; Pequignot, M.; et al. SPACR Encoded by IMPG1 Is Essential for Photoreceptor Survival by Interplaying between the Interphotoreceptor Matrix and the Retinal Pigment Epithelium. Genes 2022, 13, 1508.
  42. Mitchell, B.; Coulter, C.; Geldenhuys, W.J.; Rhodes, S.; Salido, E.M. Interphotoreceptor Matrix Proteoglycans IMPG1 and IMPG2 Proteolyze in the SEA Domain and Reveal Localization Mutual Dependency. Sci. Rep. 2022, 12, 15535.
  43. Olivier, G.; Corton, M.; Intartaglia, D.; Verbakel, S.K.; Sergouniotis, P.I.; Le Meur, G.; Dhaenens, C.-M.; Naacke, H.; Avila-Fernández, A.; Hoyng, C.B.; et al. Pathogenic Variants in IMPG1 Cause Autosomal Dominant and Autosomal Recessive Retinitis Pigmentosa. J. Med. Genet. 2021, 58, 570–578.
  44. Williams, B.N.; Draper, A.; Lang, P.F.; Lewis, T.R.; Smith, A.L.; Mayerl, S.J.; Rougié, M.; Simon, J.M.; Arshavsky, V.Y.; Greenwald, S.H.; et al. Heterogeneity in the Progression of Retinal Pathologies in Mice Harboring Patient Mimicking Impg2 Mutations. Hum. Mol. Genet. 2023, ddad199.
  45. Birtel, J.; Caswell, R.; De Silva, S.R.; Herrmann, P.; Rehman, S.; Lotery, A.J.; Mahroo, O.A.; Michaelides, M.; Webster, A.R.; MacLaren, R.E.; et al. IMPG2-Related Maculopathy. Am. J. Ophthalmol. 2024, 258, 32–42.
  46. Ribarich, N.; Rivolta, M.C.; Sacconi, R.; Querques, G. Novel IMPG2 Variant Causing Adult Macular Vitelliform Dystrophy: A Case Report. Eur. J. Ophthalmol. 2023. Online First.
  47. Hwang, S.; Kang, S.W.; Jang, J.-H.; Kim, S.J. Genetic and Clinical Characteristics of PROM1-Related Retinal Degeneration in Korean. Sci. Rep. 2023, 13, 21877.
  48. Shigesada, N.; Shikada, N.; Shirai, M.; Toriyama, M.; Higashijima, F.; Kimura, K.; Kondo, T.; Bessho, Y.; Shinozuka, T.; Sasai, N. Combination of Blockade of Endothelin Signalling and Compensation of IGF1 Expression Protects the Retina from Degeneration. Cell. Mol. Life Sci. CMLS 2024, 81, 51.
  49. Chen, T.; Xiong, Y.; Deng, C.; Hu, C.; Li, M.; Quan, R.; Yu, X. NDRG2 Alleviates Photoreceptor Apoptosis by Regulating the STAT3/TIMP3/MMP Pathway in Mice with Retinal Degenerative Disease. FEBS J. 2023. Early View.
  50. Lähteenoja, L.; Häkli, S.; Tuupanen, S.; Kuismin, O.; Palosaari, T.; Rahikkala, E.; Falck, A. A Novel Frameshift Variant in CEP78 Associated with Nonsyndromic Retinitis Pigmentosa, and a Review of CEP78-Related Phenotypes. Ophthalmic Genet. 2022, 43, 152–158.
  51. Boon, C.J.F.; Klevering, B.J.; Cremers, F.P.M.; Zonneveld-Vrieling, M.N.; Theelen, T.; Den Hollander, A.I.; Hoyng, C.B. Central Areolar Choroidal Dystrophy. Ophthalmology 2009, 116, 771–782.
  52. Corral-Serrano, J.C.; Lamers, I.J.C.; van Reeuwijk, J.; Duijkers, L.; Hoogendoorn, A.D.M.; Yildirim, A.; Argyrou, N.; Ruigrok, R.A.A.; Letteboer, S.J.F.; Butcher, R.; et al. PCARE and WASF3 Regulate Ciliary F-Actin Assembly That Is Required for the Initiation of Photoreceptor Outer Segment Disk Formation. Proc. Natl. Acad. Sci. USA 2020, 117, 9922–9931.
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.
Upload a video for this entry
Information
Subjects: Ophthalmology
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
Francesco Ruggeri
,
Chiara Ciancimino
,
Antonio Guillot
,
Daniele Fumi
,
Federico Di Tizio
,
Serena Fragiotta
,
Solmaz Abdolrahimzadeh
View Times: 105
Revisions: 2 times (View History)
Update Date: 29 Feb 2024
Table of Contents
    1000/1000
    Hot Most Recent
    Video Production Service
    Feedback