Role of Retinal Pigment Epithelium: Comparison
Please note this is a comparison between Version 3 by Peter Tang and Version 2 by Peter Tang.

The retinal pigment epithelium (RPE), situated upon Bruch’s membrane, plays multiple roles in the ocular system by interacting with photoreceptors and. Therefore, dysfunction of the RPE causes diseases related to vision loss, such as age-related macular degeneration (AMD). 

  • age-related macular degeneration
  • retinal pigment epithelium
Please wait, diff process is still running!

References

  1. Strauss, O. The retinal pigment epithelium in visual function. Physiol. Rev. 2005, 85, 845–881.
  2. Wong, W.L.; Su, X.; Li, X.; Cheung, C.M.G.; Klein, R.; Cheng, C.-Y.; Wong, T.Y. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: A systematic review and meta-analysis. Lancet Glob. Health 2014, 2, e106–e116.
  3. Klein, R.; Klein, B.E.; Linton, K.L. Prevalence of age-related maculopathy: The Beaver Dam Eye Study. Ophthalmology 1992, 99, 933–943.
  4. Mitchell, P.; Liew, G.; Gopinath, B.; Wong, T.Y. Age-related macular degeneration. Lancet 2018, 392, 1147–1159.
  5. Handa, J.T.; Rickman, C.B.; Dick, A.D.; Gorin, M.B.; Miller, J.W.; Toth, C.A.; Ueffing, M.; Zarbin, M.; Farrer, L.A. A systems biology approach towards understanding and treating non-neovascular age-related macular degeneration. Nat. Commun. 2019, 10, 1–11.
  6. Hageman, G.S.; Gehrs, K.; Johnson, L.V.; Anderson, D. Age-related macular degeneration (AMD). N. Engl. J. Med. 2008, 358, 2606–2617.
  7. Chen, M.; Luo, C.; Zhao, J.; Devarajan, G.; Xu, H. Immune regulation in the aging retina. Prog. Retin. Eye Res. 2019, 69, 159–172.
  8. Rozing, M.P.; Durhuus, J.A.; Nielsen, M.K.; Subhi, Y.; Kirkwood, T.B.; Westendorp, R.G.; Sørensen, T.L. Age-related macular degeneration: A two-level model hypothesis. Prog. Retin. Eye Res. 2020, 76, 100825.
  9. Kokotas, H.; Grigoriadou, M.; Petersen, M.B. Age-related macular degeneration: Genetic and clinical findings. Clin. Chem. Lab. Med. 2011, 49, 601–616.
  10. Bourla, D.H.; Young, T.A. Age-related macular degeneration: A practical approach to a Challenging Disease. J. Am. Geriatr. Soc. 2006, 54, 1130–1135.
  11. Age-Related Eye Disease Study Research Group. A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 8. Arch. Ophthalmol. 2001, 119, 1417–1436.
  12. Age-Related Eye Disease Study Research Group. Risk factors associated with age-related macular degeneration: A case-control study in the age-related eye disease study: Age-related eye disease study report number 3. Ophthalmology 2000, 107, 2224–2232.
  13. Davis, M.D.; Gangnon, R.E.; Lee, L.Y.; Hubbard, L.D.; Klein, B.; Klein, R.; Ferris, F.L.; Bressler, S.B.; Milton, R.C. The Age-Related Eye Disease Study severity scale for age-related macular degeneration: AREDS report No. 17. Arch. Ophthalmol. 2005, 123, 1484–1498.
  14. Sunness, J.S.; Gonzalez-Baron, J.; Applegate, C.A.; Bressler, N.M.; Tian, Y.; Hawkins, B.; Barron, Y.; Bergman, A. Enlargement of atrophy and visual acuity loss in the geographic atrophy form of age-related macular degeneration. Ophthalmology 1999, 106, 1768–1779.
  15. Wong, C.W.; Liao, J.; Cheung, G.C.; Khor, C.C.; Vithana, E.N.; Wang, J.J.; Mitchell, P.; Aung, T.; Wong, T.Y.; Cheng, C.-Y. Lens status influences the association between CFH polymorphisms and age-related macular degeneration: Findings from two population-based studies in Singapore. PloS ONE 2015, 10, e0119570.
  16. Hogan, M.; Alvarado, J.; Weddell, J. Histology of the human eye. Phila. Saunders 1971.
  17. Marshall, J. The ageing retina: Physiology or pathology. Eye 1987, 1, 282–295.
  18. Streeten, B.W. Development of the human retinal pigment epithelium and the posterior segment. Arch. Ophthalmol. 1969, 81, 383–394.
  19. Boulton, M.; Dayhaw-Barker, P. The role of the retinal pigment epithelium: Topographical variation and ageing changes. Eye 2001, 15, 384–389.
  20. Baehr, W.; PALCZEWSKI, K.; WU, S.M.; BIRD, A.C. The retinoid cycle and retina disease. Vis. Res. (Oxford) 2003, 43, 2957–2958.
  21. Ach, T.; Huisingh, C.; McGwin, G.; Messinger, J.D.; Zhang, T.; Bentley, M.J.; Gutierrez, D.B.; Ablonczy, Z.; Smith, R.T.; Sloan, K.R.; et al. Quantitative autofluorescence and cell density maps of the human retinal pigment epithelium. Investig. Ophthalmol. Vis. Sci. 2014, 55, 4832–4841.
  22. Ishibashi, K.; Tian, J.; Handa, J.T. Similarity of mRNA phenotypes of morphologically normal macular and peripheral retinal pigment epithelial cells in older human eyes. Investig. Ophthalmol. Vis. Sci. 2004, 45, 3291–3301.
  23. Gao, H.; Hollyfield, J. Aging of the human retina. Differential loss of neurons and retinal pigment epithelial cells. Investig. Ophthalmol. Vis. Sci. 1992, 33, 1–17.
  24. Del Priore, L.V.; Kuo, Y.-H.; Tezel, T.H. Age-related changes in human RPE cell density and apoptosis proportion in situ. Investig. Ophthalmol. Vis. Sci. 2002, 43, 3312–3318.
  25. Feeney-Burns, L.; Hilderbrand, E.; Eldridge, S. Aging human RPE: Morphometric analysis of macular, equatorial, and peripheral cells. Investig. Ophthalmol. Vis. Sci. 1984, 25, 195–200.
  26. Caceres, P.S.; Benedicto, I.; Lehmann, G.L.; Rodriguez-Boulan, E.J. Directional fluid transport across organ–blood barriers: Physiology and cell biology. Cold Spring Harb. Perspect. Biol. 2017, 9, a027847.
  27. Bhutto, I.; Lutty, G. Understanding age-related macular degeneration (AMD): Relationships between the photoreceptor/retinal pigment epithelium/Bruch’s membrane/choriocapillaris complex. Mol. Asp. Med. 2012, 33, 295–317.
  28. Miller, S.S.; Steinberg, R.H. Active transport of ions across frog retinal pigment epithelium. Exp. Eye Res. 1977, 25, 235–248.
  29. Ved, N.; Hulse, R.P.; Bestall, S.M.; Donaldson, L.F.; Bainbridge, J.W.; Bates, D.O. Vascular endothelial growth factor-A165b ameliorates outer-retinal barrier and vascular dysfunction in the diabetic retina. Clin. Sci. 2017, 131, 1225–1243.
  30. Desjardins, D.M.; Yates, P.W.; Dahrouj, M.; Liu, Y.; Crosson, C.E.; Ablonczy, Z. Progressive early breakdown of retinal pigment epithelium function in hyperglycemic rats. Investig. Ophthalmol. Vis. Sci. 2016, 57, 2706–2713.
  31. Farjood, F.; Vargis, E. Physical disruption of cell–cell contact induces VEGF expression in RPE cells. Mol. Vis. 2017, 23, 431.
  32. Rózanowska, M.; Jarvis-Evans, J.; Korytowski, W.; Boulton, M.E.; Burke, J.M.; Sarna, T.J. Blue light-induced reactivity of retinal age pigment: IN vitro generation OF oxygen-reactive species (∗). J. Biol. Chem. 1995, 270, 18825–18830.
  33. Różanowska, M.; Wessels, J.; Boulton, M.; Burke, J.M.; Rodgers, M.A.; Truscott, T.G.; Sarna, T. Blue light-induced singlet oxygen generation by retinal lipofuscin in non-polar media. Free Radic. Biol. Med. 1998, 24, 1107–1112.
  34. Hu, D.N.; Simon, J.D.; Sarna, T. Role of ocular melanin in ophthalmic physiology and pathology. Photochem. Photobiol. 2008, 84, 639–644.
  35. Handa, J.T. How does the macula protect itself from oxidative stress? Mol. Asp. Med. 2012, 33, 418–435.
  36. Kurtz, J.; Jones, D.; Sternberg, P.; Wu, M.; Olsen, W. Antioxidant functions of glutathione in human retinal pigment epithelium in relation to age-related macular degeneration. In Retinal Pigment Epithelium and Macular Diseases; Springer: Berlin, Germany, 1998; pp. 47–57.
  37. deS Senanayake, P.; Calabro, A.; Hu, J.G.; Bonilha, V.L.; Darr, A.; Bok, D.; Hollyfield, J.G. Glucose utilization by the retinal pigment epithelium: Evidence for rapid uptake and storage in glycogen, followed by glycogen utilization. Exp. Eye Res. 2006, 83, 235–246.
  38. Shadrach, K.; Senanayake, P.; Nishiyama, K.; Lee, J.; Hu, J.; Calabro, A.; Bok, D.; Hollyfield, J. Glucose utilization by human RPE cultures. Investig. Ophthalmol. Vis. Sci. 2003, 44, 394.
  39. Khatami, M.; Stramm, L.E.; Rookey, J.H. Ascorbate transport in cultured cat retinal pigment epithelial cells. Exp. Eye Res. 1986, 43, 607–615.
  40. Bazan, N.G.; Gordon, W.C.; de Turco, E.B.R. Docosahexaenoic acid uptake and metabolism in photoreceptors: Retinal conservation by an efficient retinal pigment epithelial cell-mediated recycling process. Neurobiol. Essent. Fat. Acids 1992, 295–306.
  41. Nagelhus, E.A.; Horio, Y.; Inanobe, A.; Fujita, A.; Haug, F.m.; Nielsen, S.; Kurachi, Y.; Ottersen, O.P. Immunogold evidence suggests that coupling of K+ siphoning and water transport in rat retinal Müller cells is mediated by a coenrichment of Kir4. 1 and AQP4 in specific membrane domains. Glia 1999, 26, 47–54.
  42. Marmor, M.F. Control of subretinal fluid: Experimental and clinical studies. Eye 1990, 4, 340–344.
  43. Miller, S.S.; Edelman, J.L. Active ion transport pathways in the bovine retinal pigment epithelium. J. Physiol. 1990, 424, 283–300.
  44. Verkman, A.; Ruiz-Ederra, J.; Levin, M.H. Functions of aquaporins in the eye. Prog. Retin. Eye Res. 2008, 27, 420–433.
  45. Erickson, K.K.; Sundstrom, J.M.; Antonetti, D.A. Vascular permeability in ocular disease and the role of tight junctions. Angiogenesis 2007, 10, 103–117.
  46. Miller, S.S.; Steinberg, R.H. Passive ionic properties of frog retinal pigment epithelium. J. Membr. Biol. 1977, 36, 337–372.
  47. Finnemann, S.C. Focal adhesion kinase signaling promotes phagocytosis of integrin-bound photoreceptors. EMBO J. 2003, 22, 4143–4154.
  48. Slomiany, M.G.; Rosenzweig, S.A. Autocrine effects of IGF-I-induced VEGF and IGFBP-3 secretion in retinal pigment epithelial cell line ARPE-19. Am. J. Physiol. Cell Physiol. 2004, 287, C746–C753.
  49. Walsh, N.; Valter, K.; Stone, J. Cellular and subcellular patterns of expression of bFGF and CNTF in the normal and light stressed adult rat retina. Exp. Eye Res. 2001, 72, 495–501.
  50. Campochiaro, P.A.; Hackett, S.F.; Vinores, S.A.; Freund, J.; Csaky, C.; LaRochelle, W.; Henderer, J.; Johnson, M.; Rodriguez, I.R.; Friedman, Z. Platelet-derived growth factor is an autocrine growth stimulator in retinal pigmented epithelial cells. J. Cell Sci. 1994, 107, 2459–2469.
  51. Ahuja, P.; Caffe, A.; Holmqvist, I.; Söderpalm, A.; Singh, D.; Shinohara, T.; Van Veen, T. Lens epithelium-derived growth factor (LEDGF) delays photoreceptor degeneration in explants of rd/rd mouse retina. Neuroreport 2001, 12, 2951–2955.
  52. Adamis, A.; Shima, D.; Yeo, K.-T.; Yeo, T.; Brown, L.; Berse, B.; Damore, P.; Folkman, J. Synthesis and secretion of vascular permeability factor/vascular endothelial growth factor by human retinal pigment epithelial cells. Biochem. Biophys. Res. Commun. 1993, 193, 631–638.
  53. Tombran-Tink, J.; Chader, G.G.; Johnson, L.V. PEDF: A pigment epithelium-derived factor with potent neuronal differentiative activity. Exp. Eye Res. 1991, 53, 411–414.
  54. Tanihara, H.; Yoshida, M.; Matsumoto, M.; Yoshimura, N. Identification of transforming growth factor-beta expressed in cultured human retinal pigment epithelial cells. Investig. Ophthalmol. Vis. Sci. 1993, 34, 413–419.
  55. Witmer, A.; Vrensen, G.; Van Noorden, C.; Schlingemann, R.O. Vascular endothelial growth factors and angiogenesis in eye disease. Prog. Retin. Eye Res. 2003, 22, 1–29.
  56. Hargrave, P.A. Rhodopsin structure, function, and topography the Friedenwald lecture. Investig. Ophthalmol. Vis. Sci. 2001, 42, 3–9.
  57. Detrick, B.; Hooks, J.J. Immune regulation in the retina. Immunol. Res. 2010, 47, 153–161.
  58. Perez, V.L.; Caspi, R.R. Immune mechanisms in inflammatory and degenerative eye disease. Trends Immunol. 2015, 36, 354–363.
  59. Zavazava, N.; Halene, M.; Westphal, E.; Nölle, B.; Duncker, G.; Eckstein, E.; Harpprecht, J.; MÜLLER-RUCHHOLTZ, W. Expression of MHC class I and II molecules by cadaver retinal pigment epithelium cells: Optimization of post-mortem HLA typing. Clin. Exp. Immunol. 1991, 84, 163–166.
  60. Xu, H.; Chen, M. Targeting the complement system for the management of retinal inflammatory and degenerative diseases. Eur. J. Pharmacol. 2016, 787, 94–104.
  61. Clark, S.J.; Bishop, P.N. The eye as a complement dysregulation hotspot. Semin. Immunopathol. 2018, 40, 65–74.
  62. Maugeri, A.; Barchitta, M.; Mazzone, M.G.; Giuliano, F.; Agodi, A. Complement system and age-related macular degeneration: Implications of gene-environment interaction for preventive and personalized medicine. BioMed Res. Int. 2018, 2018, 7532507.
  63. Park, Y.-G.; Park, Y.-S.; Kim, I.-B. Complement System and Potential Therapeutics in Age-Related Macular Degeneration. Int. J. Mol. Sci. 2021, 22, 6851.
  64. Crabb, J.W.; Miyagi, M.; Gu, X.; Shadrach, K.; West, K.A.; Sakaguchi, H.; Kamei, M.; Hasan, A.; Yan, L.; Rayborn, M.E. Drusen proteome analysis: An approach to the etiology of age-related macular degeneration. Proc. Nat. Acad. Sci. USA 2002, 99, 14682–14687.
  65. Anderson, D.H.; Radeke, M.J.; Gallo, N.B.; Chapin, E.A.; Johnson, P.T.; Curletti, C.R.; Hancox, L.S.; Hu, J.; Ebright, J.N.; Malek, G.; et al. The pivotal role of the complement system in aging and age-related macular degeneration: Hypothesis re-visited. Prog. Retin. Eye Res. 2010, 29, 95–112.
  66. Lechner, J.; Chen, M.; Hogg, R.E.; Toth, L.; Silvestri, G.; Chakravarthy, U.; Xu, H. Higher plasma levels of complement C3a, C4a and C5a increase the risk of subretinal fibrosis in neovascular age-related macular degeneration. Immun. Ageing 2016, 13, 1–9.
  67. Nozaki, M.; Raisler, B.J.; Sakurai, E.; Sarma, J.V.; Barnum, S.R.; Lambris, J.D.; Chen, Y.; Zhang, K.; Ambati, B.K.; Baffi, J.Z. Drusen complement components C3a and C5a promote choroidal neovascularization. Proc. Natl. Acad. Sci. USA 2006, 103, 2328–2333.
  68. Lipo, E.; Cashman, S.M.; Kumar-Singh, R. Aurintricarboxylic acid inhibits complement activation, membrane attack complex, and choroidal neovascularization in a model of macular degeneration. Investig. Ophthalmol. Vis. Sci. 2013, 54, 7107–7114.
  69. Schramm, E.C.; Clark, S.J.; Triebwasser, M.P.; Raychaudhuri, S.; Seddon, J.M.; Atkinson, J.P. Genetic variants in the complement system predisposing to age-related macular degeneration: A review. Mol. Immunol. 2014, 61, 118–125.
  70. Fritsche, L.G.; Chen, W.; Schu, M.; Yaspan, B.L.; Yu, Y.; Thorleifsson, G.; Zack, D.J.; Arakawa, S.; Cipriani, V.; Ripke, S. Seven new loci associated with age-related macular degeneration. Nat. Genet. 2013, 45, 433–439.
  71. Lin, M.K.; Yang, J.; Hsu, C.W.; Gore, A.; Bassuk, A.G.; Brown, L.M.; Colligan, R.; Sengillo, J.D.; Mahajan, V.B.; Tsang, S.H. HTRA 1, an age-related macular degeneration protease, processes extracellular matrix proteins EFEMP 1 and TSP 1. Aging Cell 2018, 17, e12710.
  72. Fukuoka, Y.; Strainic, M.; Medof, M. Differential cytokine expression of human retinal pigment epithelial cells in response to stimulation by C5a. Clin. Exp. Immunol. 2003, 131, 248–253.
  73. Yang, P.; Baciu, P.; Kerrigan, B.C.P.; Etheridge, M.; Sung, E.; Toimil, B.A.; Berchuck, J.E.; Jaffe, G.J. Retinal pigment epithelial cell death by the alternative complement cascade: Role of membrane regulatory proteins, calcium, PKC, and oxidative stress. Investig. Ophthalmol. Vis. Sci. 2014, 55, 3012–3021.
  74. Joseph, K.; Kulik, L.; Coughlin, B.; Kunchithapautham, K.; Bandyopadhyay, M.; Thiel, S.; Thielens, N.M.; Holers, V.M.; Rohrer, B.J. Oxidative stress sensitizes retinal pigmented epithelial (RPE) cells to complement-mediated injury in a natural antibody-, lectin pathway-, and phospholipid epitope-dependent manner. J. Biol. Chem. 2013, 288, 12753–12765.
  75. Lau, L.-I.; Chiou, S.-H.; Liu, C.J.-L.; Yen, M.-Y.; Wei, Y.-H. The effect of photo-oxidative stress and inflammatory cytokine on complement factor H expression in retinal pigment epithelial cells. Investig. Ophthalmol. Vis. Sci. 2011, 52, 6832–6841.
  76. Thurman, J.M.; Renner, B.; Kunchithapautham, K.; Ferreira, V.P.; Pangburn, M.K.; Ablonczy, Z.; Tomlinson, S.; Holers, V.M.; Rohrer, B.J. Oxidative stress renders retinal pigment epithelial cells susceptible to complement-mediated injury. J. Biol. Chem. 2009, 284, 16939–16947.
  77. Terluk, M.R.; Kapphahn, R.J.; Soukup, L.M.; Gong, H.; Gallardo, C.; Montezuma, S.R.; Ferrington, D.A. Investigating mitochondria as a target for treating age-related macular degeneration. J. Neurosci. 2015, 35, 7304–7311.
  78. Brown, E.E.; DeWeerd, A.J.; Ildefonso, C.J.; Lewin, A.S.; Ash, J.D. Mitochondrial oxidative stress in the retinal pigment epithelium (RPE) led to metabolic dysfunction in both the RPE and retinal photoreceptors. Redox Biol. 2019, 24, 101201.
  79. Fisher, C.R.; Ferrington, D.A. Perspective on AMD pathobiology: A bioenergetic crisis in the RPE. Investig. Ophthalmol. Vis. Sci. 2018, 59, AMD41–AMD47.
  80. Adijanto, J.; Du, J.; Moffat, C.; Seifert, E.L.; Hurley, J.B.; Philp, N.J. The retinal pigment epithelium utilizes fatty acids for ketogenesis: Implications for metabolic coupling with the outer retina. J. Biol. Chem. 2014, 289, 20570–20582.
  81. Toms, M.; Burgoyne, T.; Tracey-White, D.; Richardson, R.; Dubis, A.M.; Webster, A.R.; Futter, C.; Moosajee, M. Phagosomal and mitochondrial alterations in RPE may contribute to KCNJ13 retinopathy. Sci. Rep. 2019, 9, 1–15.
  82. King, A.; Gottlieb, E.; Brooks, D.G.; Murphy, M.P.; Dunaief, J.L. Mitochondria-derived Reactive Oxygen Species Mediate Blue Light-induced Death of Retinal Pigment Epithelial Cells. Photochem. Photobiol. 2004, 79, 470–475.
  83. Liang, F.-Q.; Godley, B.F. Oxidative stress-induced mitochondrial DNA damage in human retinal pigment epithelial cells: A possible mechanism for RPE aging and age-related macular degeneration. Exp. Eye Res. 2003, 76, 397–403.
  84. Karunadharma, P.P.; Nordgaard, C.L.; Olsen, T.W.; Ferrington, D.A. Mitochondrial DNA damage as a potential mechanism for age-related macular degeneration. Investig. Ophthalmol. Vis. Sci. 2010, 51, 5470–5479.
  85. Kaarniranta, K.; Pawlowska, E.; Szczepanska, J.; Jablkowska, A.; Blasiak, J. Role of mitochondrial DNA damage in ROS-mediated pathogenesis of age-related macular degeneration (AMD). Int. J. Mol. Sci. 2019, 20, 2374.
  86. Starkov, A.A. The role of mitochondria in reactive oxygen species metabolism and signaling. Ann. N.Y. Acad. Sci. 2008, 1147, 37.
  87. Kasahara, E.; Lin, L.-R.; Ho, Y.-S.; Reddy, V.N. SOD2 protects against oxidation-induced apoptosis in mouse retinal pigment epithelium: Implications for age-related macular degeneration. Investig. Ophthalmol. Vis. Sci. 2005, 46, 3426–3434.
  88. Lascaratos, G.; Ji, D.; Wood, J.P.; Osborne, N.N. Visible light affects mitochondrial function and induces neuronal death in retinal cell cultures. Vis. Res. 2007, 47, 1191–1201.
  89. Jarrett, S.G.; Lewin, A.S.; Boulton, M.E. The importance of mitochondria in age-related and inherited eye disorders. Ophthalmic Res. 2010, 44, 179–190.
  90. Candas, D.; Li, J.J. MnSOD in oxidative stress response-potential regulation via mitochondrial protein influx. Antioxid. Redox Signal. 2014, 20, 1599–1617.
  91. Nita, M.; Grzybowski, A. The role of the reactive oxygen species and oxidative stress in the pathomechanism of the age-related ocular diseases and other pathologies of the anterior and posterior eye segments in adults. Oxid. Med. Cell. Longev. 2016, 2016, 3164734.
  92. Godley, B.F.; Shamsi, F.A.; Liang, F.-Q.; Jarrett, S.G.; Davies, S.; Boulton, M.J. Blue light induces mitochondrial DNA damage and free radical production in epithelial cells. J. Biol. Chem. 2005, 280, 21061–21066.
  93. Newsholme, P.; Haber, E.; Hirabara, S.; Rebelato, E.; Procopio, J.; Morgan, D.; Oliveira-Emilio, H.; Carpinelli, A.; Curi, R. Diabetes associated cell stress and dysfunction: Role of mitochondrial and non-mitochondrial ROS production and activity. J. physiol. 2007, 583, 9–24.
  94. Hanus, J.; Anderson, C.; Wang, S. RPE necroptosis in response to oxidative stress and in AMD. Ageing Res. Rev. 2015, 24, 286–298.
  95. Man, S.M.; Karki, R.; Kanneganti, T.D. Molecular mechanisms and functions of pyroptosis, inflammatory caspases and inflammasomes in infectious diseases. Immunol. Rev. 2017, 277, 61–75.
  96. Hanus, J.; Zhang, H.; Wang, Z.; Liu, Q.; Zhou, Q.; Wang, S. Induction of necrotic cell death by oxidative stress in retinal pigment epithelial cells. Cell Death Dis. 2013, 4, e965.
  97. Guang-Yu, L.; Bin, F.; Zheng, Y.-C. Calcium overload is a critical step in programmed necrosis of ARPE-19 cells induced by high-concentration H2O2. Biomed. Environ. Sci. 2010, 23, 371–377.
  98. Elmore, S. Apoptosis: A review of programmed cell death. Toxicol. Pathol. 2007, 35, 495–516.
  99. Reed, J.C. Mechanisms of apoptosis. Am. J. Pathol. 2000, 157, 1415–1430.
  100. Kaneko, H.; Dridi, S.; Tarallo, V.; Gelfand, B.D.; Fowler, B.J.; Cho, W.G.; Kleinman, M.E.; Ponicsan, S.L.; Hauswirth, W.W.; Chiodo, V.A. DICER1 deficit induces Alu RNA toxicity in age-related macular degeneration. Nature 2011, 471, 325–330.
  101. Ho, D.T.; Bardwell, A.J.; Grewal, S.; Iverson, C.; Bardwell, L. Interacting JNK-docking sites in MKK7 promote binding and activation of JNK mitogen-activated protein kinases. J. Biol. Chem. 2006, 281, 13169–13179.
  102. Gao, J.; Cui, J.Z.; To, E.; Cao, S.; Matsubara, J.A. Evidence for the activation of pyroptotic and apoptotic pathways in RPE cells associated with NLRP3 inflammasome in the rodent eye. J. Neuroinflamm. 2018, 15, 1–12.
  103. Tseng, W.A.; Thein, T.; Kinnunen, K.; Lashkari, K.; Gregory, M.S.; D'Amore, P.A.; Ksander, B.R. NLRP3 inflammasome activation in retinal pigment epithelial cells by lysosomal destabilization: Implications for age-related macular degeneration. Investig. Ophthalmol. Vis. Sci. 2013, 54, 110–120.
  104. Cai, J.; Nelson, K.C.; Wu, M.; Sternberg, P., Jr.; Jones, D.P. Oxidative damage and protection of the RPE. Prog. Retin. Eye Res. 2000, 19, 205–221.
  105. Brandstetter, C.; Patt, J.; Holz, F.G.; Krohne, T.U. Inflammasome priming increases retinal pigment epithelial cell susceptibility to lipofuscin phototoxicity by changing the cell death mechanism from apoptosis to pyroptosis. J. Photochem. Photobiol. B Biol. 2016, 161, 177–183.
  106. Kivinen, N. The Role of Autophagy in Age-Related Macular Degeneration (AMD)–Studies into the Pathogenesis of AMD. Ph.D. dissertation, University of Michigan, Ann Arbor, MI, USA, 2018.
  107. Kaarniranta, K.; Tokarz, P.; Koskela, A.; Paterno, J.; Blasiak, J. Autophagy regulates death of retinal pigment epithelium cells in age-related macular degeneration. Cell Biol. Toxicol. 2017, 33, 113–128.
  108. Mitter, S.K.; Rao, H.V.; Qi, X.; Cai, J.; Sugrue, A.; Dunn, W.A.; Grant, M.B.; Boulton, M.E. Autophagy in the retina: A potential role in age-related macular degeneration. Retin. Degener. Dis. 2012, 83–90.
  109. Krohne, T.U.; Stratmann, N.K.; Kopitz, J.; Holz, F.G. Effects of lipid peroxidation products on lipofuscinogenesis and autophagy in human retinal pigment epithelial cells. Exp. Eye Res. 2010, 90, 465–471.
  110. Wang, A.L.; Lukas, T.J.; Yuan, M.; Du, N.; Tso, M.O.; Neufeld, A.H. Autophagy and exosomes in the aged retinal pigment epithelium: Possible relevance to drusen formation and age-related macular degeneration. PloS ONE 2009, 4, e4160.
  111. Alge, C.S.; Priglinger, S.G.; Neubauer, A.S.; Kampik, A.; Zillig, M.; Bloemendal, H.; Welge-Lussen, U. Retinal pigment epithelium is protected against apoptosis by αB-crystallin. Investig. Ophthalmol. Vis. Sci. 2002, 43, 3575–3582.
  112. Gangalum, R.K.; Schibler, M.J.; Bhat, S.P. Small heat shock protein αB-crystallin is part of cell cycle-dependent Golgi reorganization. J. Biol. Chem. 2004, 279, 43374–43377.
  113. De, S.; Rabin, D.M.; Salero, E.; Lederman, P.L.; Temple, S.; Stern, J.H. Human retinal pigment epithelium cell changes and expression of αB-crystallin: A biomarker for retinal pigment epithelium cell change in age-related macular degeneration. Arch. Ophthalmol. 2007, 125, 641–645.
  114. Kannan, R.; Sreekumar, P.G.; Hinton, D.R. Alpha crystallins in the retinal pigment epithelium and implications for the pathogenesis and treatment of age-related macular degeneration. Biochim. Biophys. Acta (BBA)-Gen. Subj. 2016, 1860, 258–268.
  115. Dimberg, A.; Rylova, S.; Dieterich, L.C.; Olsson, A.-K.; Schiller, P.; Wikner, C.; Bohman, S.; Botling, J.; Lukinius, A.; Wawrousek, E.F. αB-crystallin promotes tumor angiogenesis by increasing vascular survival during tube morphogenesis. J. Am. Soc. Hematol. 2008, 111, 2015–2023.
  116. Kase, S.; He, S.; Sonoda, S.; Kitamura, M.; Spee, C.; Wawrousek, E.; Ryan, S.J.; Kannan, R.; Hinton, D.R. αB-crystallin regulation of angiogenesis by modulation of VEGF. J. Am. Soc. Hematol. 2010, 115, 3398–3406.
  117. Yaung, J.; Kannan, R.; Wawrousek, E.F.; Spee, C.; Sreekumar, P.G.; Hinton, D.R. Exacerbation of retinal degeneration in the absence of alpha crystallins in an in vivo model of chemically induced hypoxia. Exp. Eye Res. 2008, 86, 355–365.
  118. Watanabe, G.; Kato, S.; Nakata, H.; Ishida, T.; Ohuchi, N.; Ishioka, C. αB-crystallin: A novel p53-target gene required for p53-dependent apoptosis. Cancer Sci. 2009, 100, 2368–2375.
  119. Li, D.W.-C.; Liu, J.-P.; Mao, Y.-W.; Xiang, H.; Wang, J.; Ma, W.-Y.; Dong, Z.; Pike, H.M.; Brown, R.E.; Reed, J.C. Calcium-activated RAF/MEK/ERK signaling pathway mediates p53-dependent apoptosis and is abrogated by αB-crystallin through inhibition of RAS activation. Mol. Biol. Cell 2005, 16, 4437–4453.
  120. Rojas, J.C.; Gonzalez-Lima, F. Low-level light therapy of the eye and brain. Eye Brain 2011, 3, 49.
  121. Tata, D.B.; Waynant, R.W. Laser therapy: A review of its mechanism of action and potential medical applications. Laser Photonics Rev. 2011, 5, 1–12.
  122. Ivandic, B.T.; Ivandic, T. Low-level laser therapy improves vision in patients with age-related macular degeneration. Photomed. Laser Surg. 2008, 26, 241–245.
  123. Merry, G.; Dotson, R.; Devenyi, R.; Markowitz, S.; Reyes, S. Photobiomodulation as a new treatment for dry age related macular degeneration. results from the toronto and Oak ridge photobimodulation study in AMD (TORPA). Investig. Ophthalmol. Vis. Sci. 2012, 53, 2049.
  124. Tang, J.; Herda, A.A.; Kern, T.S. Photobiomodulation in the treatment of patients with non-center-involving diabetic macular oedema. Br. J. Ophthalmol. 2014, 98, 1013–1015.
  125. Fuma, S.; Murase, H.; Kuse, Y.; Tsuruma, K.; Shimazawa, M.; Hara, H. Photobiomodulation with 670 nm light increased phagocytosis in human retinal pigment epithelial cells. Mol. Vis. 2015, 21, 883.
  126. Lavey, B.J.; Estlack, L.E.; Schuster, K.J.; Rockwell, B.A.; Wigle, J.C. The response of human retinal pigmented epithelial cells in vitro to changes in nitric oxide concentration stimulated by low levels of red light. Proceedings of Mechanisms for Low-Light Therapy VIII, San Francisco, CA, USA, 2–3 February 2013; p. 85690.
  127. Kokkinopoulos, I.; Colman, A.; Hogg, C.; Heckenlively, J.; Jeffery, G. Age-related retinal inflammation is reduced by 670 nm light via increased mitochondrial membrane potential. Neurobiol. Aging 2013, 34, 602–609.
  128. Merry, G.F.; Munk, M.R.; Dotson, R.S.; Walker, M.G.; Devenyi, R.G. Photobiomodulation reduces drusen volume and improves visual acuity and contrast sensitivity in dry age-related macular degeneration. Acta Ophthalmol. 2017, 95, e270–e277.
  129. Tezel, T.H.; Del Priore, L.V.; Berger, A.S.; Kaplan, H.J. Adult retinal pigment epithelial transplantation in exudative age-related macular degeneration. Am. J. Ophthalmol. 2007, 143, 584–595.
  130. Binder, S.; Krebs, I.; Hilgers, R.-D.; Abri, A.; Stolba, U.; Assadoulina, A.; Kellner, L.; Stanzel, B.V.; Jahn, C.; Feichtinger, H.; et al. Outcome of transplantation of autologous retinal pigment epithelium in age-related macular degeneration: A prospective trial. Investig. Ophthalmol. Vis. Sci. 2004, 45, 4151–4160.
  131. Lu, Y.; Han, L.; Wang, C.; Dou, H.; Feng, X.; Hu, Y.; Feng, K.; Wang, X.; Ma, Z. A comparison of autologous transplantation of retinal pigment epithelium (RPE) monolayer sheet graft with RPE–Bruch's membrane complex graft in neovascular age-related macular degeneration. Acta Ophthalmol. 2017, 95, e443–e452.
  132. Kamao, H.; Mandai, M.; Okamoto, S.; Sakai, N.; Suga, A.; Sugita, S.; Kiryu, J.; Takahashi, M. Characterization of human induced pluripotent stem cell-derived retinal pigment epithelium cell sheets aiming for clinical application. Stem Cell Rep. 2014, 2, 205–218.
  133. Nakagawa, M.; Koyanagi, M.; Tanabe, K.; Takahashi, K.; Ichisaka, T.; Aoi, T.; Okita, K.; Mochiduki, Y.; Takizawa, N.; Yamanaka, S. Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts. Nat. Biotechnol. 2008, 26, 101–106.
  134. da Cruz, L.; Fynes, K.; Georgiadis, O.; Kerby, J.; Luo, Y.H.; Ahmado, A.; Vernon, A.; Daniels, J.T.; Nommiste, B.; Hasan, S.M. Phase 1 clinical study of an embryonic stem cell–derived retinal pigment epithelium patch in age-related macular degeneration. Nat. Biotechnol. 2018, 36, 328–337.
  135. Surendran, H.; Nandakumar, S.; Stoddard, J.; Mohan, V.; Upadhyay, P.K.; McGill, T.J.; Pal, R. Therapy. 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 Rep. 2021, 12, 1–17.
  136. Shrestha, R.; Wen, Y.-T.; Tsai, R.-K. Effective differentiation and biological characterization of retinal pigment epithelium derived from human induced pluripotent stem cells. Curr. Eye Res. 2020, 45, 1155–1167.
  137. Sharma, R.; Khristov, V.; Rising, A.; Jha, B.S.; Dejene, R.; Hotaling, N.; Li, Y.; Stoddard, J.; Stankewicz, C.; Wan, Q. Clinical-grade stem cell–derived retinal pigment epithelium patch rescues retinal degeneration in rodents and pigs. Sci. Trans. Med. No. 475 (eaat550). 2019, 11.
  138. Mandai, M.; Watanabe, A.; Kurimoto, Y.; Hirami, Y.; Morinaga, C.; Daimon, T.; Fujihara, M.; Akimaru, H.; Sakai, N.; Shibata, Y. Autologous induced stem-cell–derived retinal cells for macular degeneration. N. Engl. J. Med. 2017, 376, 1038–1046.
  139. Schwartz, S.D.; Regillo, C.D.; Lam, B.L.; Eliott, D.; Rosenfeld, P.J.; Gregori, N.Z.; Hubschman, J.-P.; Davis, J.L.; Heilwell, G.; Spirn, M. Human embryonic stem cell-derived retinal pigment epithelium in patients with age-related macular degeneration and Stargardt's macular dystrophy: Follow-up of two open-label phase 1/2 studies. Lancet 2015, 385, 509–516.
  140. Schwartz, S.D.; Tan, G.; Hosseini, H.; Nagiel, A. Subretinal transplantation of embryonic stem cell–derived retinal pigment epithelium for the treatment of macular degeneration: An assessment at 4 years. Investig. Ophthalmol. Vis. Sci. 2016, 57, ORSFc1–ORSFc9.
  141. Kashani, A.H.; Lebkowski, J.S.; Rahhal, F.M.; Avery, R.L.; Salehi-Had, H.; Dang, W.; Lin, C.-M.; Mitra, D.; Zhu, D.; Thomas, B.B. A bioengineered retinal pigment epithelial monolayer for advanced, dry age-related macular degeneration. Sci. Trans. Med. No. 435 (eaao4097). 2018, 10.
More
Video Production Service