Progress toward the maintenance and repair of degenerating retinal circuitry

Retina

Volumn 30, Issue 7, 2010, Pages 983-1001

  Vugler, Anthony A ^a  

^a UNIVERSITY COLLEGE LONDON   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

MELANOPSIN;

CELL SURVIVAL; CELL TRANSPLANTATION; GENE MUTATION; GENE THERAPY; HISTOPATHOLOGY; HUMAN; LEBER CONGENITAL AMAUROSIS; PHOTORECEPTOR; PIGMENT EPITHELIUM; PROSTHESIS; RETINA AMACRINE CELL; RETINA BIPOLAR GANGLION CELL; RETINA CONE; RETINA DEGENERATION; RETINA DISEASE; RETINA MACULA AGE RELATED DEGENERATION; RETINA ROD; RETINITIS PIGMENTOSA; REVIEW; VISION;

HUMANS; PHOTORECEPTOR CELLS, VERTEBRATE; RETINAL DEGENERATION; VISUAL PATHWAYS;

EID: 77954700761     PISSN: 0275004X     EISSN: None     Source Type: Journal    
DOI: 10.1097/IAE.0b013e3181e2a680     Document Type: Review

References (180)

1. Arshavsky VY, Lamb TD, Pugh EN Jr. G proteins and phototransduction. Annu Rev Physiol 2002;64:153-187.
2. Jin M, Li S, Moghrabi WN, et al. Rpe65 is the retinoid isomerase in bovine retinal pigment epithelium. Cell 2005; 122:449-459.
3. Moiseyev G, Chen Y, Takahashi Y, et al. RPE65 is the isomerohydrolase in the retinoid visual cycle. Proc Natl Acad Sci U S A 2005;102:12413-12418.
4. Redmond TM, Poliakov E, Yu S, et al. Mutation of key residues of RPE65 abolishes its enzymatic role as isomerohydrolase in the visual cycle. Proc Natl Acad Sci U S A 2005;102:13658-13663.
5. Mata NL, Radu RA, Clemmons RC, Travis GH. Isomerization and oxidation of vitamin a in cone-dominant retinas: a novel pathway for visual-pigment regeneration in daylight. Neuron 2002;36:69-80.
6. Seeliger MW, Grimm C, Stahlberg F, et al. New views on RPE65 deficiency: the rod system is the source of vision in a mouse model of Leber congenital amaurosis. Nat Genet 2001;29:70-74.
7. Cai X, Conley SM, Naash MI. RPE65: role in the visual cycle, human retinal disease, and gene therapy. Ophthalmic Genet 2009;30:57-62.
8. Jacobson SG, Aleman TS, Cideciyan AV, et al. Human cone photoreceptor dependence on RPE65 isomerase. Proc Natl Acad Sci U S A 2007;104:15123-15128.
9. Hamel CP, Tsilou E, Harris E, et al. A developmentally regulated microsomal protein specific for the pigment epithelium of the vertebrate retina. J Neurosci Res 1993;34: 414-425.
10. Porto FB, Perrault I, Hicks D, et al. Prenatal human ocular degeneration occurs in Leber's congenital amaurosis (LCA1 and 2). Adv Exp Med Biol 2003;533:59-68.
11. Chalupa LM, Gunhan E. Development of On and Off retinal pathways and retinogeniculate projections. Prog Retin Eye Res 2004;23:31-51.
12. Nomura A, Shigemoto R, Nakamura Y, et al. Developmentally regulated postsynaptic localization of a metabotropic glutamate receptor in rat rod bipolar cells. Cell 1994;77:361-369.
13. DeVries SH. Bipolar cells use kainate and AMPA receptors to filter visual information into separate channels. Neuron 2000; 28:847-856.
14. Munch TA, Da Silveira RA, Siegert S, et al. Approach sensitivity in the retina processed by a multifunctional neural circuit. Nat Neurosci 2009;12:1308-1316.
15. ProvencioI,RollagMD,CastrucciAM.Photoreceptivenet inthe mammalian retina. This mesh of cells may explain how some blind mice can still tell day from night. Nature 2002;415:493.
16. Provencio I, Rodriguez IR, Jiang G, et al. A novel human opsin in the inner retina. J Neurosci 2000;20:600-605.
17. Berson DM, Dunn FA, Takao M. Phototransduction by retinal ganglion cells that set the circadian clock. Science 2002;295: 1070-1073.
18. Lucas RJ, Douglas RH, Foster RG. Characterization of an ocular photopigment capable of driving pupillary constriction in mice. Nat Neurosci 2001;4:621-626.
19. Lucas RJ, Freedman MS, Munoz M, et al. Regulation of the mammalian pineal by non-rod, non-cone, ocular photoreceptors. Science 1999;284:505-507. (Pubitemid 29289627)
20. Foster RG, Provencio I, Hudson D, et al. Circadian photoreception in the retinally degenerate mouse (rd/rd). J Comp Physiol A 1991;169:39-50.
21. Provencio I, Wong S, Lederman AB, et al. Visual and circadian responses to light in aged retinally degenerate mice. Vision Res 1994;34:1799-1806.
22. Semo M, Lupi D, Peirson SN, et al. Light-induced c-fos in melanopsin retinal ganglion cells of young and aged rodless/ coneless (rd/rd cl) mice. Eur J Neurosci 2003;18:3007-3017.
23. Hattar S, Liao HW, Takao M, et al. Melanopsin-containing retinal ganglion cells: architecture, projections, and intrinsic photosensitivity. Science 2002;295:1065-1070.
24. Hattar S, Kumar M, Park A, et al. Central projections of melanopsin-expressing retinal ganglion cells in the mouse. J Comp Neurol 2006;497:326-349.
25. Gooley JJ, Lu J, Fischer D, Saper CB. A broad role for melanopsin in nonvisual photoreception. J Neurosci 2003;23: 7093-7106.
26. DoMT, Kang SH, XueT, et al. Photon capture and signalling by melanopsin retinal ganglion cells. Nature 2009;457:281-287.
27. Melyan Z, Tarttelin EE, Bellingham J, et al. Addition of human melanopsin renders mammalian cells photoresponsive. Nature 2005;433:741-745.
28. Isoldi MC, Rollag MD, Castrucci AM, Provencio I. Rhabdomeric phototransduction initiated by the vertebrate photopigment melanopsin. Proc Natl Acad Sci U S A 2005; 102:1217-1221.
29. Doyle SE, Castrucci AM, McCall M, et al. Nonvisual light responses in the Rpe65 knockout mouse: rod loss restores sensitivity to the melanopsin system. Proc Natl Acad Sci U S A 2006;103:10432-10437.
30. Tu DC, Owens LA, Anderson L, et al. Inner retinal photoreception independent of the visual retinoid cycle. Proc Natl Acad Sci U S A 2006;103:10426-10431.
31. Pires SS, Hughes S, Turton M, et al. Differential expression of two distinct functional isoforms of melanopsin (Opn4) in the mammalian retina. J Neurosci 2009;29:12332-12342.
32. Schmidt TM, Kofuji P. Functional and morphological differences among intrinsically photosensitive retinal ganglion cells. J Neurosci 2009;29:476-482.
33. Viney TJ, Balint K, Hillier D, et al. Local retinal circuits of melanopsin-containing ganglion cells identified by transsynaptic viral tracing. Curr Biol 2007;17:981-988.
34. Dacey DM, Liao HW, Peterson BB, et al. Melanopsinexpressing ganglion cells in primate retina signal colour and irradiance and project to the LGN. Nature 2005;433:749-754.
35. Dkhissi-Benyahya O, Rieux C, Hut RA, Cooper HM. Immunohistochemical evidence of a melanopsin cone in human retina. Invest Ophthalmol Vis Sci 2006;47:1636-1641.
36. Zaidi FH, Hull JT, Peirson SN, et al. Short-wavelength light sensitivity of circadian, pupillary, and visual awareness in humans lacking an outer retina. Curr Biol 2007;17:2122-2128.
37. Hattar S, Ecker J, Dumitrescu O, et al. Functions and target innervations of distinct subtypes of melanopsin cells. ARVO annual meeting 2009:5027.
38. Noseda R, Kainz V, Jakubowski M, et al. A neural mechanism for exacerbation of headache by light. Nat Neurosci 2010;13: 239-245.
39. Jusuf PR, Lee SC, Hannibal J, Grunert U. Characterization and synaptic connectivity of melanopsin-containing ganglion cells in the primate retina. Eur J Neurosci 2007;26:2906-2921. (Pubitemid 350119791)
40. Belenky MA, Smeraski CA, Provencio I, et al. Melanopsin retinal ganglion cells receive bipolar and amacrine cell synapses. J Comp Neurol 2003;460:380-393.
41. Vugler AA, Redgrave P, Semo M, et al. Dopamine neurones form a discrete plexus with melanopsin cells in normal and degenerating retina. Exp Neurol 2007;205:26-35.
42. Nguyen-Legros J.Morphology and distribution of catecholamineneurons in mammalian retina. Prog Retin Res 1988;7:114-147.
43. Cameron MA, Pozdeyev N, Vugler AA, et al. Light regulation of retinal dopamine that is independent of melanopsin phototransduction. Eur J Neurosci 2009;29:761-767.
44. Zhang DQ, Zhou TR, McMahon DG. Functional heterogeneity of retinal dopaminergic neurons underlying their multiple roles in vision. J Neurosci 2007;27:692-699.
45. Zhang DQ, Wong KY, Sollars PJ, et al. Intraretinal signaling by ganglion cell photoreceptors to dopaminergic amacrine neurons. Proc Natl Acad Sci USA 2008;105:14181-14186.
46. Dumitrescu ON, Pucci FG, Wong KY, Berson DM. Ectopic retinal ON bipolar cell synapses in the OFF inner plexiform layer: contacts with dopaminergic amacrine cells and melanopsin ganglion cells. J Comp Neurol 2009;517:226-244.
47. Hoshi H, Liu WL, Massey SC, Mills SL. ON inputs to the OFF layer: bipolar cells that break the stratification rules of the retina. J Neurosci 2009;29:8875-8883.
48. Bowes C, Li T, Danciger M, et al. Retinal degeneration in the rd mouse is caused by a defect in the beta subunit of rod cGMP-phosphodiesterase. Nature 1990;347:677-680.
49. Carter-Dawson LD, LaVail MM, Sidman RL. Differential effect of the rd mutation on rods and cones in the mouse retina. Invest Ophthalmol Vis Sci 1978;17:489-498.
50. Strettoi E, Pignatelli V. Modifications of retinal neurons in a mouse model of retinitis pigmentosa. Proc Natl Acad Sci U S A 2000;97:11020-11025.
51. Strettoi E, Porciatti V, Falsini B, et al. Morphological and functional abnormalities in the inner retina of the rd/rd mouse. J Neurosci 2002;22:5492-5504.
52. Lin B, Masland RH, Strettoi E. Remodeling of cone photoreceptor cells after rod degeneration in rd mice. Exp Eye Res 2009;88:589-599.
53. Punzo C, Kornacker K, Cepko CL. Stimulation of the insulin/ mTOR pathway delays cone death in a mouse model of retinitis pigmentosa. Nat Neurosci 2009;12:44-52.
54. Jimenez AJ, Garcia-Fernandez JM,Gonzalez B, FosterRG. The spatio-temporal pattern of photoreceptor degeneration in the aged rd/rd mouse retina. Cell Tissue Res 1996;284:193-202.
55. D'Cruz PM, Yasumura D, Weir J, et al. Mutation of the receptor tyrosine kinase gene Mertk in the retinal dystrophic RCS rat. Hum Mol Genet 2000;9:645-651.
56. Semo M, Vugler AA, Jeffery G. Paradoxical opsin expressing cells in the inner retina that are augmented following retinal degeneration. Eur J Neurosci 2007;25:2296-2306.
57. Wang S, Lu B, Lund RD. Morphological changes in the Royal CollegeofSurgeons rat retinaduringphotoreceptordegeneration and after cell-based therapy. J CompNeurol 2005;491:400-417.
58. Haverkamp S, Michalakis S, Claes E, et al. Synaptic plasticity in CNGA3(-/-) mice: cone bipolar cells react on the missing cone input and form ectopic synapses with rods. J Neurosci 2006;26:5248-5255.
59. Cuenca N, Pinilla I, Sauve Y, et al. Regressive and reactive changes in the connectivity patterns of rod and cone pathways of P23H transgenic rat retina. Neuroscience 2004;127:301-317.
60. Cuenca N, Pinilla I, SauveY, Lund R. Early changes in synaptic connectivity following progressive photoreceptor degeneration in RCS rats. Eur J Neurosci 2005;22:1057-1072.
61. Biel M, Seeliger M, Pfeifer A, et al. Selective loss of cone function in mice lacking the cyclic nucleotide-gated channel CNG3. Proc Natl Acad Sci U S A 1999;96:7553-7557.
62. Michalakis S, Geiger H, Haverkamp S, et al. Impaired opsin targeting and cone photoreceptor migration in the retina of mice lacking the cyclic nucleotide-gated channel CNGA3. Invest Ophthalmol Vis Sci 2005;46:1516-1524. (Pubitemid 41685898)
63. Marc RE, Jones BW, Anderson JR, et al. Neural reprogramming in retinal degeneration. Invest Ophthalmol Vis Sci 2007; 48:3364-3371.
64. Chua J, Fletcher EL, Kalloniatis M. Functional remodeling of glutamate receptors byinner retinal neurons occurs froman early stage of retinaldegeneration. JCompNeurol2009;514:473-491.
65. Gerth C, Delahunt PB, Alam S, et al. Cone-mediated multifocal electroretinogram in age-related macular degeneration: progression over a long-term follow-up. Arch Ophthalmol 2006;124:345-352.
66. Curcio CA, Millican CL, Allen KA, Kalina RE. Aging of the human photoreceptor mosaic: evidence for selective vulnerability of rods in central retina. Invest Ophthalmol Vis Sci 1993;34:3278-3296.
67. Jackson GR, Owsley C, Cordle EP, Finley CD. Aging and scotopic sensitivity. Vision Res 1998;38:3655-3662.
68. Leveillard T, Mohand-Said S, Lorentz O, et al. Identification and characterization of rod-derived cone viability factor. Nat Genet 2004;36:755-759.
69. Yang Y, Mohand-Said S, Danan A, et al. Functional cone rescue by RdCVF protein in a dominant model of retinitis pigmentosa. Mol Ther 2009;17:787-795.
70. Parker RO, Fan J, Nickerson JM, et al. Normal cone function requires the interphotoreceptor retinoid binding protein. J Neurosci 2009;29:4616-4621.
71. Cronin T, Leveillard T, Sahel JA. Retinal degenerations: from cell signaling to cell therapy; pre-clinical and clinical issues. Curr Gene Ther 2007;7:121-129.
72. Pinilla I, Lund RD, Sauve Y. Enhanced cone dysfunction in rats homozygous for the P23H rhodopsin mutation. Neurosci Lett 2005;382:16-21.
73. Machida S,Raz-Prag D,FarissRN, et al. PhotopicERGnegative response from amacrine cell signaling in RCS rat retinal degeneration. Invest Ophthalmol Vis Sci 2008;49:442-452.
74. Bush RA, Hawks KW, Sieving PA. Preservation of inner retinal responses in the aged Royal College of Surgeons rat. Evidence against glutamate excitotoxicity in photoreceptor degeneration. Invest Ophthalmol Vis Sci 1995;36:2054-2062.
75. Pinilla I, Lund RD, Sauve Y. Cone function studied with flicker electroretinogram during progressive retinal degeneration in RCS rats. Exp Eye Res 2005;80:51-59.
76. Greferath U, Goh HC, Chua PY, et al. Mapping retinal degeneration and loss of function in Rd-FTL mice. Invest Ophthalmol Vis Sci 2009;50:5955-5964.
77. Panda S, Provencio I, Tu DC, et al. Melanopsin is required for non-image-forming photic responses in blind mice. Science 2003;301:525-527.
78. Girman SV, Wang S, Lund RD. Time course of deterioration of rod and cone function in RCS rat and the effects of subretinal cell grafting: a light- and dark-adaptation study. Vision Res 2005;45:343-354.
79. Vugler AA, Redgrave P, Hewson-Stoate NJ, et al. Constant illumination causes spatially discrete dopamine depletion in the normal and degenerate retina. J ChemNeuroanat 2007;33:9-22.
80. Sakamoto K, Liu C, Tosini G. Classical photoreceptors regulate melanopsin mRNA levels in the rat retina. J Neurosci 2004;24:9693-9697.
81. Vugler AA, Semo M, Joseph A, Jeffery G. Survival and remodeling of melanopsin cells during retinal dystrophy. Vis Neurosci 2008;25:125-138.
82. Villegas-Perez MP, Lawrence JM, Vidal-Sanz M, et al. Ganglion cell loss in RCS rat retina: a result of compression of axons by contracting intraretinal vessels linked to the pigment epithelium. J Comp Neurol 1998;392:58-77.
83. Eisenfeld AJ, LaVail MM, LaVail JH. Assessment of possible transneuronal changes in the retina of rats with inherited retinal dystrophy: cell size, number, synapses, and axonal transport by retinal ganglion cells. J Comp Neurol 1984;223:22-34.
84. Grafstein B, Murray M, Ingoglia NA. Protein synthesis and axonal transport in retinal ganglion cells of mice lacking visual receptors. Brain Res 1972;44:37-48.
85. Wang S, Villegas-Perez MP, Vidal-Sanz M, Lund RD. Progressive optic axon dystrophy and vascular changes in rd mice. Invest Ophthalmol Vis Sci 2000;41:537-545.
86. Mazzoni F, Novelli E, Strettoi E. Retinal ganglion cells survive and maintain normal dendritic morphology in a mouse model of inherited photoreceptor degeneration. J Neurosci 2008;28:14282-14292.
87. Vugler AA, Coffey PJ. Loss of calretinin immunoreactive fibers in subcortical visual recipient structures of the RCS dystrophic rat. Exp Neurol 2003;184:464-478.
88. Vugler A, Lawrence J, Walsh J, et al. Embryonic stem cells and retinal repair. Mech Dev 2007;124:807-829.
89. Jones BW, Marc RE. Retinal remodeling during retinal degeneration. Exp Eye Res 2005;81:123-137.
90. Pascolini D, Mariotti SP, Pokharel GP, et al. 2002 global update of available data on visual impairment: a compilation of population-based prevalence studies. Ophthalmic Epidemiol 2004;11:67-115.
91. Congdon N, O'Colmain B, Klaver CC, et al. Causes and prevalence of visual impairment among adults in the United States. Arch Ophthalmol 2004;122:477-485. (Pubitemid 38456282)
92. Jager RD, Mieler WF, Miller JW. Age-related macular degeneration. N Engl J Med 2008;358:2606-2617.
93. Midena E, Vujosevic S, Convento E, et al. Microperimetry and fundus autofluorescence in patients with early age-related macular degeneration. Br J Ophthalmol 2007;91:1499-1503.
94. Jackson GR, Owsley C, Curcio CA. Photoreceptor degeneration and dysfunction in aging and age-related maculopathy. Ageing Res Rev 2002;1:381-396.
95. Klein R, Klein BE, Jensen SC, Meuer SM. The five-year incidence and progression of age-related maculopathy: the Beaver Dam Eye Study. Ophthalmology 1997;104:7-21. (Pubitemid 27081937)
96. Curcio CA, Medeiros NE, Millican CL. Photoreceptor loss in age-related macular degeneration. Invest Ophthalmol Vis Sci 1996;37:1236-1249.
97. Medeiros NE, Curcio CA. Preservation of ganglion cell layer neurons in age-related macular degeneration. Invest Ophthalmol Vis Sci 2001;42:795-803.
98. Milam AH, Jacobson SG. Photoreceptor rosettes with blue cone opsin immunoreactivity in retinitis pigmentosa. Ophthalmology 1990;97:1620-1631.
99. Wu KH, Madigan MC, Billson FA, Penfold PL. Differential expression of GFAP in early v late AMD: a quantitative analysis. Br J Ophthalmol 2003;87:1159-1166.
100. Ethen CM, Feng X, Olsen TW, Ferrington DA. Declines in arrestin and rhodopsin in the macula with progression of agerelated macular degeneration. Invest Ophthalmol Vis Sci 2005;46:769-775.
101. Gupta N, Brown KE, Milam AH. Activated microglia in human retinitis pigmentosa, late-onset retinal degeneration, and age-related macular degeneration. Exp Eye Res 2003;76: 463-471.
102. Shelley EJ, Madigan MC, Natoli R, et al. Cone degeneration in aging and age-related macular degeneration. Arch Ophthalmol 2009;127:483-492.
103. Li ZY, Kljavin IJ, Milam AH. Rod photoreceptor neurite sprouting in retinitis pigmentosa. J Neurosci 1995;15:5429-15238
104. Luhmann UF, Robbie S, Munro PM, et al.The drusen-like phenotype in aging Ccl2 knockout mice is caused by an accelerated accumulation of swollen autofluorescent subretinal macrophages. Invest Ophthalmol Vis Sci 2009;50: 5934-5943.
105. Ramirez JM, Ramirez AI, Salazar JJ, et al. Changes of astrocytes in retinal ageing and age-related macular degeneration. Exp Eye Res 2001;73:601-615.
106. Curcio CA, Allen KA. Topography of ganglion cells in human retina. J Comp Neurol 1990;300:5-25.
107. Lafaut BA, Aisenbrey S, Vanden Broecke C, Bartz-Schmidt KU. Clinicopathological correlation of deep retinal vascular anomalous complex in age related macular degeneration. Br J Ophthalmol 2000;84:1269-1274.
108. Hartnett ME,Weiter JJ, Staurenghi G, Elsner AE. Deep retinal vascular anomalous complexes in advanced age-related macular degeneration. Ophthalmology 1996;103:2042-2053.
109. Newman NM, Stevens RA, Heckenlively JR. Nerve fibre layer loss in diseases of the outer retinal layer. Br J Ophthalmol 1987;71:21-26.
110. Aleman TS, Soumittra N, Cideciyan AV, et al. CERKL mutations cause an autosomal recessive cone-rod dystrophy with inner retinopathy. Invest Ophthalmol Vis Sci 2009;50: 5944-5954.
111. Santos A, Humayun MS, De Juan E Jr, et al. Preservation of the inner retina in retinitis pigmentosa. A morphometric analysis. Arch Ophthalmol 1997;115:511-515.
112. Stone JL, Barlow WE, Humayun MS, et al. Morphometric analysis of macular photoreceptors and ganglion cells in retinas with retinitis pigmentosa. Arch Ophthalmol 1992;110: 1634-1639.
113. den Hollander AI, Roepman R, Koenekoop RK, Cremers FP. Leber congenital amaurosis: genes, proteins and disease mechanisms. Prog Retin Eye Res 2008;27:391-419.
114. Redmond TM, Yu S, Lee E, et al. Rpe65 is necessary for production of 11-cis-vitamin A in the retinal visual cycle. Nat Genet 1998;20:344-351.
115. Pang JJ, Chang B, Hawes NL, et al. Retinal degeneration 12 (rd12): a new, spontaneously arising mouse model for human Leber congenital amaurosis (LCA). Mol Vis 2005;11: 152-162.
116. Aguirre GD, Baldwin V, Pearce-Kelling S, et al. Congenital stationary night blindness in the dog: common mutation in the RPE65 gene indicates founder effect. Mol Vis 1998;4:23.
117. Fan J, Rohrer B, Moiseyev G, et al. Isorhodopsin rather than rhodopsin mediates rod function in RPE65 knock-out mice. Proc Natl Acad Sci U S A 2003;100:13662-13667.
118. Rohrer B, Lohr HR, Humphries P, et al. Cone opsin mislocalization in Rpe65-/- mice: a defect that can be corrected by 11-cis retinal. Invest Ophthalmol Vis Sci 2005;46:3876-3882.
119. Znoiko SL, Rohrer B, Lu K, et al. Downregulation of conespecific gene expression and degeneration of cone photoreceptors in the Rpe65-/- mouse at early ages. Invest Ophthalmol Vis Sci 2005;46:1473-1479.
120. Maeda T, Cideciyan AV, Maeda A, et al. Loss of cone photoreceptors caused by chromophore depletion is partially prevented by the artificial chromophore pro-drug, 9-cisretinyl acetate. Hum Mol Genet 2009;18:2277-2287.
121. Zhang H, Fan J, Li S, et al. Trafficking of membraneassociated proteins to cone photoreceptor outer segments requires the chromophore 11-cis-retinal. J Neurosci 2008;28: 4008-4014.
122. Rohrer B, Goletz P, Znoiko S, et al. Correlation of regenerable opsin with rod ERG signal in Rpe65-/- mice during development and aging. Invest Ophthalmol Vis Sci 2003; 44:310-315.
123. Fu Y, Zhong H, Wang MH, et al. Intrinsically photosensitive retinal ganglion cells detect light with a vitamin A-based photopigment, melanopsin. Proc Natl Acad Sci U S A 2005; 102:10339-10344.
124. McCall MA, Gregg RG, Merriman K, et al. Morphological and physiological consequences of the selective elimination of rod photoreceptors in transgenic mice. Exp Eye Res 1996; 63:35-50.
125. Jacobson SG, Cideciyan AV, Aleman TS, et al. Photoreceptor layer topography in children with Leber congenital amaurosis caused by RPE65 mutations. Invest Ophthalmol Vis Sci 2008; 49:4573-4577.
126. Jacobson SG, Aleman TS, Cideciyan AV, et al. Identifying photoreceptors in blind eyes caused by RPE65 mutations: prerequisite for human gene therapy success. Proc Natl Acad Sci U S A 2005;102:6177-6182.
127. Maeda T, Maeda A, Leahy P, et al. Effects of long-term administration of 9-cis-retinyl acetate on visual function in mice. Invest Ophthalmol Vis Sci 2009;50:322-333.
128. Simonelli F, Ziviello C, Testa F, et al. Clinical and molecular genetics of Leber's congenital amaurosis: a multicenter study of Italian patients. Invest Ophthalmol Vis Sci 2007;48: 4284-4290.
129. Jacobson SG, Aleman TS, Cideciyan AV, et al. Defining the residual vision in Leber congenital amaurosis caused by RPE65 mutations. Invest Ophthalmol Vis Sci 2009;50: 2368-2375.
130. Samardzija M, von Lintig J, Tanimoto N, et al. R91W mutation in Rpe65 leads to milder early-onset retinal dystrophy due to the generation of low levels of 11-cisretinal. Hum Mol Genet 2008;17:281-292.
131. Holz FG, Bindewald-Wittich A, Fleckenstein M, et al. Progression of geographic atrophy and impact of fundus autofluorescence patterns in age-related macular degeneration. Am J Ophthalmol 2007;143:463-472.
132. Del Priore LV, Tezel TH, Kaplan HJ. Maculoplasty for age-related macular degeneration: reengineering Bruch's membrane and the human macula. Prog Retin Eye Res 2006; 25:539-562.
133. Da Cruz L, Chen FK, Ahmado A, et al. RPE transplantation and its role in retinal disease. Prog RetinEyeRes 2007;26:598-635.
134. Chen FK, Patel PJ, Uppal GS, et al. A comparison of macular translocationwithpatchgraft inneovascular age-relatedmacular degeneration. Invest Ophthalmol Vis Sci 2009;50:1848-1855.
135. Van Meurs JC, Van Den Biesen PR. Autologous retinal pigment epithelium and choroid translocation in patients with exudative age-related macular degeneration: short-term follow-up. Am J Ophthalmol 2003;136:688-695.
136. Lu B, Malcuit C,Wang S, et al. Long-term safety and function of RPE from human embryonic stem cells in preclinical models of macular degeneration. Stem Cells 2009;27: 2126-2135.
137. Lund RD, Wang S, Klimanskaya I, et al. Human embryonic stem cell-derived cells rescue visual function in dystrophic RCS rats. Cloning Stem Cells 2006;8:189-199.
138. Vugler A, Carr AJ, Lawrence J, et al. Elucidating the phenomenon of HESC-derived RPE: anatomy of cell genesis, expansion and retinal transplantation. Exp Neurol 2008;214: 347-361.
139. IdelsonM,Alper R, ObolenskyA, et al. Directed differentiation of human embryonic stem cells into functional retinal pigment epithelium cells. Cell Stem Cell 2009;5:396-408.
140. Carr AJ, Vugler AA, Hikita ST, et al. Protective effects of human iPS-derived retinal pigment epithelium cell transplantation in the retinal dystrophic rat. PLoS One 2009;4:e8152.
141. Buchholz DE, Hikita ST, Rowland TJ, et al. Derivation of functional retinal pigmented epithelium from induced pluripotent stem cells. Stem Cells 2009;27:2427-2434.
142. Sieving PA, Caruso RC, Tao W, et al. Ciliary neurotrophic factor (CNTF) for human retinal degeneration: phase I trial of CNTF delivered by encapsulated cell intraocular implants. Proc Natl Acad Sci U S A 2006;103:3896-3901.
143. Bennett J, Tanabe T, Sun D, et al. Photoreceptor cell rescue in retinal degeneration (rd) mice by in vivo gene therapy. Nat Med 1996;2:649-654.
144. Ali RR, Sarra GM, Stephens C, et al. Restoration of photoreceptor ultrastructure and function in retinal degeneration slow mice by gene therapy. Nat Genet 2000;25:306-310.
145. Cai X, Nash Z, Conley SM, et al. A partial structural and functional rescue of a retinitis pigmentosa model with compacted DNA nanoparticles. PLoS One 2009;4:e5290.
146. Maguire AM, High KA, Auricchio A, et al. Age-dependent effects of RPE65 gene therapy for Leber's congenital amaurosis: a phase 1 dose-escalation trial. Lancet 2009;374:1597-1605.
147. Simonelli F, Maguire AM, Testa F, et al. Gene therapy for Leber's congenital amaurosis is safe and effective through 1.5 years after vector administration. Mol Ther 2009;18:643-650.
148. Acland GM, Aguirre GD, Ray J, et al. Gene therapy restores vision in a canine model of childhood blindness. Nat Genet 2001;28:92-95.
149. Acland GM, Aguirre GD, Bennett J, et al. Long-term restoration of rod and cone vision by single dose rAAVmediated gene transfer to the retina in a canine model of childhood blindness. Mol Ther 2005;12:1072-1082.
150. Dejneka NS, Surace EM, Aleman TS, et al. In utero gene therapy rescues vision in a murine model of congenital blindness. Mol Ther 2004;9:182-188.
151. Maguire AM, Simonelli F, Pierce EA, et al. Safety and efficacy of gene transfer for Leber's congenital amaurosis. N Engl J Med 2008;358:2240-2248.
152. Hauswirth WW, Aleman TS, Kaushal S, et al. Treatment of Leber congenital amaurosis due to RPE65 mutations by ocular subretinal injection of adeno-associated virus gene vector: short-term results of a phase I trial. Hum Gene Ther 2008;19:979-990.
153. Bainbridge JW, Smith AJ, Barker SS, et al. Effect of gene therapy on visual function in Leber's congenital amaurosis. N Engl J Med 2008;358:2231-2239.
154. Cideciyan AV, Aleman TS, Boye SL, et al. Human gene therapy for RPE65 isomerase deficiency activates the retinoid cycle of vision but with slow rod kinetics. Proc Natl Acad Sci U S A 2008;105:15112-15117.
155. Cideciyan AV, Hauswirth WW, Aleman TS, et al. Human RPE65 gene therapy for Leber congenital amaurosis: persistence of early visual improvements and safety at 1 year. Hum Gene Ther 2009;20:999-1004.
156. Cideciyan AV, Hauswirth WW, Aleman TS, et al. Vision 1 year after gene therapy for Leber's congenital amaurosis. N Engl J Med 2009;361:725-727.
157. Samardzija M, Tanimoto N, Kostic C, et al. In conditions of limited chromophore supply rods entrap 11-cis-retinal leading to loss of cone function and cell death. Hum Mol Genet 2009;18:1266-1275.
158. Smith AJ, Bainbridge JW, Ali RR. Prospects for retinal gene replacement therapy. Trends Genet 2009;25:156-165.
159. Allocca M, Doria M, Petrillo M, et al. Serotype-dependent packaging of large genes in adeno-associated viral vectors results in effective gene delivery in mice. J Clin Invest 2008; 118:1955-1964.
160. MacLaren RE, Pearson RA, MacNeil A, et al. Retinal repair by transplantation of photoreceptor precursors. Nature 2006; 444:203-207.
161. Bartsch U, Oriyakhel W, Kenna PF, et al. Retinal cells integrate into the outer nuclear layer and differentiate into mature photoreceptors after subretinal transplantation into adult mice. Exp Eye Res 2008;86:691-700.
162. West EL, Pearson RA, Tschernutter M, et al. Pharmacological disruption of the outer limiting membrane leads to increased retinal integration of transplanted photoreceptor precursors. Exp Eye Res 2008;86:601-611.
163. Kwan AS, Wang S, Lund RD. Photoreceptor layer reconstruction in a rodent model of retinal degeneration. Exp Neurol 1999;159:21-33.
164. Lamba DA, Gust J, Reh TA. Transplantation of human embryonic stemcell-derivedphotoreceptors restores somevisual function in Crx-deficient mice. Cell Stem Cell 2009;4:73-79.
165. Jomary C, Jones SE, Lotery A. Generation of light-sensitive photoreceptor phenotypes by genetic modification of human adult ocular stem cells using Crx. Invest Ophthalmol Vis Sci 2009;51:1181-1189.
166. Pu M, Xu L, Zhang H. Visual response properties of retinal ganglion cells in the royal college of surgeons dystrophic rat. Invest Ophthalmol Vis Sci 2006;47:3579-3585.
167. Stasheff SF. Emergence of sustained spontaneous hyperactivity and temporary preservation of OFF responses in ganglion cells of the retinal degeneration (rd1) mouse. J Neurophysiol 2008;99:1408-1421.
168. Margolis DJ, Newkirk G, Euler T, Detwiler PB. Functional stability of retinal ganglion cells after degeneration-induced changes in synaptic input. J Neurosci 2008;28:6526-6536.
169. HumayunMS, De Juan E Jr,Weiland JD, et al. Pattern electrical stimulationof thehuman retina.VisionRes1999;39:2569-2576.
170. De Balthasar C, Patel S, Roy A, et al. Factors affecting perceptual thresholds in epiretinal prostheses. Invest Ophthalmol Vis Sci 2008;49:2303-2314.
171. Hegemann P. Algal sensory photoreceptors. Annu Rev Plant Biol 2008;59:167-189.
172. Foster KW, Saranak J, Patel N, et al. A rhodopsin is the functional photoreceptor for phototaxis in the unicellular eukaryote Chlamydomonas. Nature 1984;311:756-759.
173. Boyden ES, Zhang F, Bamberg E, et al. Millisecondtimescale, genetically targeted optical control of neural activity. Nat Neurosci 2005;8:1263-1268.
174. Bi A, Cui J, Ma YP, et al. Ectopic expression of a microbialtype rhodopsin restores visual responses in mice with photoreceptor degeneration. Neuron 2006;50:23-33.
175. Lagali PS, Balya D, Awatramani GB, et al. Light-activated channels targeted to ON bipolar cells restore visual function in retinal degeneration. Nat Neurosci 2008;11:667-675.
176. Zhang Y, Ivanova E, Bi A, Pan ZH. Ectopic expression of multiple microbial rhodopsins restores ON and OFF light responses in retinas with photoreceptor degeneration. J Neurosci 2009;29:9186-9196.
177. Tomita H, Sugano E, Yawo H, et al. Restoration of visual response in aged dystrophic RCS rats using AAV-mediated channelopsin-2 gene transfer. Invest Ophthalmol Vis Sci 2007;48:3821-3826.
178. Tomita H, Sugano E, Isago H, et al. Channelrhodopsin-2 gene transduced into retinal ganglion cells restores functional vision in genetically blind rats. Exp Eye Res 2009;90:429-436.
179. Tomita H, Sugano E, Fukazawa Y, et al. Visual properties of transgenic rats harboring the channelrhodopsin-2 gene regulated by the thy-1.2 promoter. PLoS One 2009;4: e7679.
180. Lin B, Koizumi A, Tanaka N, et al. Restoration of visual function in retinal degeneration mice by ectopic expression of melanopsin. Proc Natl Acad Sci U S A 2008;105:16009-16014.