Leber congenital amaurosis due to RPE65 mutations and its treatment with gene therapy

Progress in Retinal and Eye Research

Volumn 29, Issue 5, 2010, Pages 398-427

  Cideciyan, Artur V ^a  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

Cortical plasticity; Electroretinogram (ERG); Functional MRI; Optical coherence tomography (OCT); Perimetry; Retinal degeneration; Retinal pigment epithelium (RPE); Rod and cone photoreceptors; RPE65; Transient pupillary light reflex (TPLR); Visual (retinoid) cycle

Indexed keywords

11 CIS RETINAL; COMPLEMENTARY DNA; LENTIVIRUS VECTOR; LIPOFUSCIN; NEOMYCIN; PARVOVIRUS VECTOR; PROTEIN RPE 65; STEROID; UNCLASSIFIED DRUG; VISUAL PIGMENT; CARRIER PROTEIN; CIS TRANS ISOMERASE; DNA; EYE PROTEIN; RETINOID ISOMEROHYDROLASE;

AUTOFLUORESCENCE; BIOCHEMISTRY; CLINICAL RESEARCH; CLINICAL TRIAL; DOG; DRUG DELIVERY SYSTEM; ELECTRORETINOGRAM; EYE FIXATION; EYE MOVEMENT; FUNCTIONAL MAGNETIC RESONANCE IMAGING; GENE EXPRESSION; GENE MUTATION; GENE REPLACEMENT THERAPY; GENE THERAPY; GENOTYPE PHENOTYPE CORRELATION; HISTOPATHOLOGY; HUMAN; LEBER CONGENITAL AMAUROSIS; LENTIVIRINAE; LIGHT; LOSS OF FUNCTION MUTATION; NONHUMAN; NUCLEAR MAGNETIC RESONANCE IMAGING; NYSTAGMUS; OPTICAL COHERENCE TOMOGRAPHY; PHOTORECEPTOR; PHOTOTRANSDUCTION; PIGMENT EPITHELIUM; PRIORITY JOURNAL; PUPIL REFLEX; RETINA DEGENERATION; RETINOPATHY; REVIEW; VIRUS RECOMBINANT; VISION; VISUAL ACUITY; VISUAL CORTEX; VISUAL DISORDER; VISUAL IMPAIRMENT; WILD TYPE; ANIMAL; GENETICS; MUTATION; PROCEDURES;

ANIMALS; CARRIER PROTEINS; DNA; EYE PROTEINS; GENE THERAPY; HUMANS; LEBER CONGENITAL AMAUROSIS; MUTATION; CIS-TRANS-ISOMERASES; GENETIC THERAPY;

EID: 77954620055     PISSN: 13509462     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.preteyeres.2010.04.002     Document Type: Review

References (224)

1. Acland G.M., Aguirre G.D., Ray J., Zhang Q., Aleman T.S., Cideciyan A.V., Pearce-Kelling S.E., Anand V., Zeng Y., Maguire A.M., et al. Gene therapy restores vision in a canine model of childhood blindness. Nat. Genet. 2001, 28:92-95.
2. Acland G.M., Aguirre G.D., Bennett J., Aleman T.S., Cideciyan A.V., Bennicelli J., Dejneka N.S., Pearce-Kelling S.E., Maguire A.M., Palczewski K., et al. Long-term restoration of rod and cone vision by single dose rAAV-mediated gene transfer to the retina in a canine model of childhood blindness. Mol. Ther. 2005, 12:1072-1082.
3. Aguirre G.D., Baldwin V., Pearce-Kelling S., Narfström K., Ray K., Acland G.M. Congenital stationary night blindness in the dog: common mutation in the RPE65 gene indicates founder effect. Mol. Vis. 1998, 4:23.
4. Aguirre G.K., Komáromy A.M., Cideciyan A.V., Brainard D.H., Aleman T.S., Roman A.J., Avants B.B., Gee J.C., Korczykowski M., Hauswirth W.W., et al. Canine and human visual cortex intact and responsive despite early retinal blindness from RPE65 mutation. PLoS Med. 2007, 4:e230.
5. Aleman T.S., LaVail M.M., Montemayor R., Ying G., Maguire M.M., Laties A.M., Jacobson S.G., Cideciyan A.V. Augmented rod bipolar cell function in partial receptor loss: an ERG study in P23H rhodopsin transgenic and aging normal rats. Vision Res. 2001, 41:2779-2797.
6. Aleman T.S., Jacobson S.G., Chico J.D., Scott M.L., Cheung A.Y., Windsor E.A.M., Furushima M., Redmond T.M., Bennett J., Palczewski K., et al. Impairment of the transient pupillary light reflex in Rpe65-/- mice and humans with Leber congenital amaurosis. Investig. Ophthalmol. Vis. Sci. 2004, 45:1259-1271.
7. Alexander J.J., Hauswirth W.W. Adeno-associated viral vectors and the retina. Adv. Exp. Med. Biol. 2008, 613:121-128.
8. Al-Khayer K., Hagstrom S., Pauer G., Zegarra H., Sears J., Traboulsi E.I. Thirty-year follow-up of a patient with leber congenital amaurosis and novel RPE65 mutations. Am. J. Ophthalmol. 2004, 137:375-377.
9. Bainbridge J.W., Smith A.J., Barker S.S., Robbie S., Henderson R., Balaggan K., Viswanathan A., Holder G.E., Stockman A., Tyler N., et al. Effect of gene therapy on visual function in Leber's congenital amaurosis. N. Engl. J. Med. 2008, 358:2231-2239.
10. Baker C.I., Peli E., Knouf N., Kanwisher N.G. Reorganization of visual processing in macular degeneration. J. Neurosci. 2005, 25:614-618.
11. Bemelmans A.P., Kostic C., Crippa S.V., Hauswirth W.W., Lem J., Munier F.L., Seeliger M.W., Wenzel A., Arsenijevic Y. Lentiviral gene transfer of RPE65 rescues survival and function of cones in a mouse model of Leber congenital amaurosis. PLoS Med. 2006, 3:e347.
12. Ben-Arie-Weintrob Y., Berson E.L., Dryja T.P. Histopathologic-genotypic correlations in retinitis pigmentosa and allied diseases. Ophthalmic Genet. 2005, 26:91-100.
13. Bennicelli J., Wright J.F., Komaromy A., Jacobs J.B., Hauck B., Zelenaia O., Mingozzi F., Hui D., Chung D., Rex T.S., et al. Reversal of blindness in animal models of leber congenital amaurosis using optimized AAV2-mediated gene transfer. Mol. Ther. 2008, 16:458-465.
14. Bereta G., Kiser P.D., Golczak M., Sun W., Heon E., Saperstein D.A., Palczewski K. Impact of retinal disease-associated RPE65 mutations on retinoid isomerization. Biochemistry 2008, 47:9856-9865.
15. Bok D. The retinal pigment epithelium: a versatile partner in vision. J. Cell Sci. Suppl. 1993, 17:189-195.
16. Butz M., Wörgötter F., van Ooyen A. Activity-dependent structural plasticity. Brain Res. Rev. 2009, 60:287-305.
17. Cai X., Conley S.M., Naash M.I. RPE65: role in the visual cycle, human retinal disease, and gene therapy. Ophthalmic Genet. 2009, 30:57-62.
18. Campochiaro P.A., Nguyen Q.D., Shah S.M., Klein M.L., Holz E., Frank R.N., Saperstein D.A., Gupta A., Stout J.T., Macko J., et al. Adenoviral vector-delivered pigment epithelium-derived factor for neovascular age-related macular degeneration: results of a phase I clinical trial. Hum. Gene, Ther. 2006, 17:167-176.
19. Carter-Dawson L.D., LaVail M.M. Rods and cones in the mouse retina. I. Structural analysis using light and electron microscopy. J. Comp. Neurol. 1979, 188:245-262.
20. Chen Y., Moiseyev G., Takahashi Y., Ma J.X. RPE65 gene delivery restores isomerohydrolase activity and prevents early cone loss in Rpe65-/- mice. Investig. Ophthalmol. Vis. Sci. 2006, 47:1177-1184.
21. Chévez-Barrios P., Chintagumpala M., Mieler W., Paysse E., Boniuk M., Kozinetz C., Hurwitz M.Y., Hurwitz R.L. Response of retinoblastoma with vitreous tumor seeding to adenovirus-mediated delivery of thymidine kinase followed by ganciclovir. J. Clin. Oncol. 2005, 23:7927-7935.
22. Cheung S.H., Legge G.E. Functional and cortical adaptations to central vision loss. Vis. Neurosci. 2005, 22:187-201.
23. Chung D.C., Lee V., Maguire A.M. Recent advances in ocular gene therapy. Curr. Opin. Ophthalmol. 2009, 20:377-381.
24. Cideciyan A.V., Jacobson S.G. An alternative phototransduction model for human rod and cone ERG a-waves: normal parameters and variation with age. Vision Res. 1996, 36:2609-2621.
25. Cideciyan A.V., Pugh E.N., Lamb T.D., Huang Y., Jacobson S.G. Rod plateaux during dark adaptation in Sorsby's fundus dystrophy and vitamin A deficiency. Investig. Ophthalmol. Vis. Sci. 1997, 38:1786-1794.
26. Cideciyan A.V., Zhao X., Nielsen L., Khani S.C., Jacobson S.G., Palczewski K. Null mutation in the rhodopsin kinase gene slows recovery kinetics of rod and cone phototransduction in man. Proc. Natl. Acad. Sci. U. S. A. 1998, 95:328-333.
27. Cideciyan A.V., Hood D.C., Huang Y., Banin E., Li Z.Y., Stone E.M., Milam A.H., Jacobson S.G. Disease sequence from mutant rhodopsin allele to rod and cone photoreceptor degeneration in man. Proc. Natl. Acad. Sci. U. S. A. 1998, 95:1703-1708.
28. Cideciyan A.V., Haeseleer F., Fariss R.N., Aleman T.S., Jang G.F., Verlinde C.L., Marmor M.F., Jacobson S.G., Palczewski K. Rod and cone visual cycle consequences of a null mutation in the 11-cis-retinol dehydrogenase gene in man. Vis. Neurosci. 2000, 17:667-678.
29. Cideciyan A.V., Aleman T.S., Swider M., Schwartz S.B., Steinberg J.D., Brucker A.J., Maguire A.M., Bennett J., Stone E.M., Jacobson S.G. Mutations in ABCA4 result in accumulation of lipofuscin before slowing of the retinoid cycle: a reappraisal of the human disease sequence. Hum. Mol. Genet. 2004, 13:525-534.
30. Cideciyan A.V., Aleman T.S., Boye S.L., Schwartz S.B., Kaushal S., Roman A.J., Pang J.J., Sumaroka A., Windsor E.A., Wilson J.M., 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.
31. Cideciyan A.V., Hauswirth W.W., Aleman T.S., Kaushal S., Schwartz S.B., Boye S.L., Windsor E.A., Conlon T.J., Sumaroka A., Pang J.J., 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.
32. Cideciyan A.V., Hauswirth W.W., Aleman T.S., Kaushal S., Schwartz S.B., Boye S.L., Windsor E.A., Conlon T.J., Sumaroka A., Roman A.J., et al. Vision 1 year after gene therapy for Leber's congenital amaurosis. N. Engl. J. Med. 2009, 361:725-727.
33. Colella P., Cotugno G., Auricchio A. Ocular gene therapy: current progress and future prospects. Trends Mol. Med. 2009, 15:23-31.
34. Conley S.M., Cai X., Naash M.I. Nonviral ocular gene therapy: assessment and future directions. Curr. Opin. Mol. Ther. 2008, 10:456-463.
35. Crossland M.D., Culham L.E., Kabanarou S.A., Rubin G.S. Preferred retinal locus development in patients with macular disease. Ophthalmology 2005, 112:1579-1585.
36. Curcio C.A., Sloan K.R., Kalina R.E., Hendrickson A.E. Human photoreceptor topography. J. Comp. Neurol. 1990, 292:497-523.
37. Dejneka N.S., Surace E.M., Aleman T.S., Cideciyan A.V., Lyubarsky A., Savchenko A., Redmond T.M., Tang W., Wei Z., Rex T.S., et al. In utero gene therapy rescues vision in a murine model of congenital blindness. Mol. Ther. 2004, 9:182-188.
38. Delori F.C., Dorey C.K., Staurenghi G., Arend O., Goger D.G., Weiter J.J. In vivo fluorescence of the ocular fundus exhibits retinal pigment epithelium lipofuscin characteristics. Investig. Ophthalmol. Vis. Sci. 1995, 36:718-729.
39. den Hollander A.I., Roepman R., Koenekoop R.K., Cremers F.P. Leber congenital amaurosis: genes, proteins and disease mechanisms. Prog. Retin. Eye Res. 2008, 27:391-419.
40. Déruaz A., Whatham A.R., Mermoud C., Safran A.B. Reading with multiple preferred retinal loci: implications for training a more efficient reading strategy. Vision Res. 2002, 42:2947-2957.
41. Déruaz A., Goldschmidt M., Whatham A.R., Mermoud C., Lorincz E.N., Schnider A., Safran A.B. A technique to train new oculomotor behavior in patients with central macular scotomas during reading related tasks using scanning laser ophthalmoscopy: immediate functional benefits and gains retention. BMC Ophthalmol 2006, 23(6):35.
42. Ding X.Q., Harry C.S., Umino Y., Matveev A.V., Fliesler S.J., Barlow R.B. Impaired cone function and cone degeneration resulting from CNGB3 deficiency: down-regulation of CNGA3 biosynthesis as a potential mechanism. Hum. Mol. Genet. 2009, 15(18):4770-4780.
43. Drexler W., Fujimoto J.G. State-of-the-art retinal optical coherence tomography. Prog. Retin. Eye Res. 2008, 27:45-88.
44. El Matri L., Ambresin A., Schorderet D.F., Kawasaki A., Seeliger M.W., Wenzel A., Arsenijevic Y., Borruat F.X., Munier F.L. Phenotype of three consanguineous Tunisian families with early-onset retinal degeneration caused by an R91W homozygous mutation in the RPE65 gene. Graefes Arch. Clin. Exp. Ophthalmol. 2006, 244:1104-1112.
45. Eldred G.E., Lasky M.R. Retinal age pigments generated by self-assembling lysosomotropic detergents. Nature 1993, 361:724-726.
46. Ellemberg D., Lewis T.L., Liu C.H., Maurer D. Development of spatial and temporal vision during childhood. Vision Res. 1999, 39:2325-2333.
47. Ellemberg D., Lewis T.L., Maurer D., Lui C.H., Brent H.P. Spatial and temporal vision in patients treated for bilateral congenital cataracts. Vision Res. 1999, 39:3480-3489.
48. Ellemberg D., Lewis T.L., Maurer D., Brent H.P. Influence of monocular deprivation during infancy on the later development of spatial and temporal vision. Vision Res. 2000, 40:3283-3295.
49. Fan J., Woodruff M.L., Cilluffo M.C., Crouch R.K., Fain G.L. Opsin activation of transduction in the rods of dark-reared Rpe65 knockout mice. J. Physiol. 2005, 568:83-95.
50. Fan J., Wu B.X., Sarna T., Rohrer B., Redmond T.M., Crouch R.K. 9-cis Retinal increased in retina of RPE65 knockout mice with decrease in coat pigmentation. Photochem. Photobiol. 2006, 82:1461-1467.
51. Feathers K.L., Lyubarsky A.L., Khan N.W., Teofilo K., Swaroop A., Williams D.S., Pugh E.N., Thompson D.A. Nrl-knockout mice deficient in Rpe65 fail to synthesize 11-cis retinal and cone outer segments. Investig. Ophthalmol. Vis. Sci. 2008, 49:1126-1135.
52. Felius J., Thompson D.A., Khan N.W., Bingham E.L., Jamison J.A., Kemp J.A., Sieving P.A. Clinical course and visual function in a family with mutations in the RPE65 gene. Arch. Ophthalmol. 2002, 120:55-61.
53. Ferris F.L., Kassoff A., Bresnick G.H., Bailey I. New visual acuity charts for clinical research. Am. J. Ophthalmol. 1982, 94:91-96.
54. Fine I., Wade A.R., Brewer A.A., May M.G., Goodman D.F., Boynton G.M., Wandell B.A., MacLeod D.I. Long-term deprivation affects visual perception and cortex. Nat. Neurosci. 2003, 6:915-916.
55. Fishman G.A., Jacobson S.G., Alexander K.R., Cideciyan A.V., Birch D.G., Weleber R.G., Hood D.C. Outcome measures and their application in clinical trials for retinal degenerative diseases: outline, review, and perspective. Retina 2005, 25:772-777.
56. Ford M., Bragadóttir R., Rakoczy P.E., Narfström K. Gene transfer in the RPE65 null mutation dog: relationship between construct volume, visual behavior and electroretinographic (ERG) results. Doc. Ophthalmol. 2003, 107:79-86.
57. Gal A., Gu S., Bremser D., Lorenz B., Apfelstedt-Sylla E., Zrenner E., Gerding H., Denton M.J., Thompson D.A. Mutation spectrum of RPE65 in autosomal recessive childhood-onset severe retinal dystrophy. Investig. Ophthalmol. Vis. Sci. 1998, 39:S901.
58. Gearhart P.M., Gearhart C.C., Petersen-Jones S.M. A novel method for objective vision testing in canine models of inherited retinal disease. Investig. Ophthalmol. Vis. Sci. 2008, 49:3568-3576.
59. Geller S.F., Lewis G.P., Fisher S.K. FGFR1, signaling, and AP-1 expression after retinal detachment: reactive Müller and RPE cells. Investig. Ophthalmol. Vis. Sci. 2001, 42:1363-1369.
60. Giannikopoulos D.V., Eysel U.T. Dynamics and specificity of cortical map reorganization after retinal lesions. Proc. Natl. Acad. Sci. U. S. A. 2006, 103:10805-10810.
61. Gilbert P.E., Pirogovsky E., Brushfield A.M., Luu T.T., Tolentino J.C., Renteria A.F. Age-related changes in associative learning for olfactory and visual stimuli in rodents. Ann. N. Y. Acad. Sci. 2009, 1170:718-724.
62. Gouras P., Kong J., Tsang S.H. Retinal degeneration and RPE transplantation in Rpe65(-/-) mice. Investig. Ophthalmol. Vis. Sci. 2002, 43:3307-3311.
63. Grimm C., Wenzel A., Hafezi F., Yu S., Redmond T.M., Remé C.E. Protection of Rpe65-deficient mice identifies rhodopsin as a mediator of light-induced retinal degeneration. Nat. Genet. 2000, 25:63-66.
64. Gu S.M., Thompson D.A., Srikumari C.R., Lorenz B., Finckh U., Nicoletti A., Murthy K.R., Rathmann M., Kumaramanickavel G., Denton M.J., et al. Mutations in RPE65 cause autosomal recessive childhood-onset severe retinal dystrophy. Nat. Genet. 1997, 17:194-197.
65. Hall E.C., Gordon J., Hainline L., Abramov I., Engber K. Childhood visual experience affects adult voluntary ocular motor control. Optom. Vis. Sci. 2000, 77:511-523.
66. Hall E.C., Ciuffreda K.J. Fixational ocular motor control is plastic despite visual deprivation. Vis. Neurosci. 2002, 19:475-481.
67. Hamann S., Schorderet D.F., Cottet S. Bax-induced apoptosis in Leber's congenital amaurosis: a dual role in rod and cone degeneration. PLoS ONE 2009, 4:e6616.
68. Hamel C.P., Griffoin J.M., Lasquellec L., Bazalgette C., Arnaud B. Retinal dystrophies caused by mutations in RPE65: assessment of visual functions. Br. J. Ophthalmol. 2001, 85:424-427.
69. Hammarrenger B., Roy M.S., Ellemberg D., Labrosse M., Orquin J., Lippe S., Lepore F. Developmental delay and magnocellular visual pathway function in very-low-birthweight preterm infants. Dev. Med. Child. Neurol. 2007, 49:28-33.
70. Hattar S., Lucas R.J., Mrosovsky N., Thompson S., Douglas R.H., Hankins M.W., Lem J., Biel M., Hofmann F., Foster R.G., et al. Melanopsin and rod-cone photoreceptive systems account for all major accessory visual functions in mice. Nature 2003, 424:75-81.
71. Hauswirth W.W., Aleman T.S., Kaushal S., Cideciyan A.V., Schwartz S.B., Wang L., Conlon T.J., Boye S.L., Flotte T.R., Byrne B.J., 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.
72. Heher K.L., Traboulsi E.I., Maumenee I.H. The natural history of Leber's congenital amaurosis. Age-related findings in 35 patients. Ophthalmology 1992, 99:241-245.
73. Hemati N., Feathers K.L., Chrispell J.D., Reed D.M., Carlson T.J., Thompson D.A. RPE65 surface epitopes, protein interactions, and expression in rod- and cone-dominant species. Mol. Vis. 2005, 11:1151-1165.
74. Henderson R., Lorenz B., Moore A.T. Clinical and molecular genetic aspects of Leber's congenital amaurosis. Pediatric Ophthalmology, Neuro-Ophthalmology, Genetics 2006, 157-177. Springer, Berlin. B. Lorenz, A.T. Moore (Eds.).
75. Hernandez, M., Pearce-Kelling, S.E., Rodriguez, F.D., Aguirre, G.D., Vecino, E. Selective alteration of the expression of retinal molecular markers in the canine RPE65 model of Leber congenital amaurosis. Invest. Ophthalmol. Vis. Sci., in press.
76. Holtmaat A., Svoboda K. Experience-dependent structural synaptic plasticity in the mammalian brain. Nat. Rev. Neurosci. 2009, 10:647-658.
77. Horsten G.P.M., Winkleman J.E. Development of the ERG in relation to histological differentiation of the retina in man and animals. Arch. Ophthalmol. 1960, 63:232-242.
78. Huang D., Swanson E.A., Lin C.P., Schuman J.S., Stinson W.G., Chang W., Hee M.R., Flotte T., Gregory K., Puliafito C.A., et al. Optical coherence tomography. Science 1991, 254:1178-1181.
79. Huang Y., Cideciyan A.V., Papastergiou G.I., Banin E., Semple-Rowland S.L., Milam A.H., Jacobson S.G. Relation of optical coherence tomography to microanatomy in normal and rd chickens. Investig. Ophthalmol. Vis. Sci. 1998, 39:2405-2416.
80. Huang Y., Cideciyan A.V., Alemán T.S., Banin E., Huang J., Syed N.A., Petters R.M., Wong F., Milam A.H., Jacobson S.G. Optical coherence tomography (OCT) abnormalities in rhodopsin mutant transgenic swine with retinal degeneration. Exp. Eye Res. 2000, 70:247-251.
81. Hubel D.H., Wiesel T.N. Receptive fields of single neurones in the cat's striate cortex. J. Physiol. 1959, 148:574-591.
82. Imanishi Y., Batten M.L., Piston D.W., Baehr W., Palczewski K. Noninvasive two-photon imaging reveals retinyl ester storage structures in the eye. J. Cell Biol. 2004, 164:373-383.
83. Jacobson S.G., Cideciyan A.V., Regunath G., Rodriguez F.J., Vandenburgh K., Sheffield V.C., Stone E.M. Night blindness in Sorsby's fundus dystrophy reversed by vitamin A. Nat. Genet. 1995, 11:27-32.
84. Jacobson S.G., Cideciyan A.V., Huang Y., Hanna D.B., Freund C.L., Affatigato L.M., Carr R.E., Zack D.J., Stone E.M., McInnes R.R. Retinal degenerations with truncation mutations in the cone-rod homeobox (CRX) gene. Investig. Ophthalmol. Vis. Sci. 1998, 39:2417-2426.
85. Jacobson S.G., Cideciyan A.V., Wright E., Wright A.F. Phenotypic marker for early disease detection in dominant late-onset retinal degeneration. Investig. Ophthalmol. Vis. Sci. 2001, 42:1882-1890.
86. Jacobson S.G., Aleman T.S., Cideciyan A.V., Sumaroka A., Schwartz S.B., Windsor E.A., Traboulsi E.I., Heon E., Pittler S.J., Milam A.H., 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.
87. Jacobson S.G., Acland G.M., Aguirre G.D., Aleman T.S., Schwartz S.B., Cideciyan A.V., Zeiss C.J., Komaromy A.M., Kaushal S., Roman A.J., et al. Safety of recombinant adeno-associated virus type 2-RPE65 vector delivered by ocular subretinal injection. Mol. Ther. 2006, 13:1074-1084.
88. Jacobson S.G., Boye S.L., Aleman T.S., Conlon T.J., Zeiss C.J., Roman A.J., Cideciyan A.V., Schwartz S.B., Komaromy A.M., Doobrajh M., et al. Safety in nonhuman primates of ocular AAV2-RPE65, a candidate treatment for blindness in Leber congenital amaurosis. Hum. Gene Ther. 2006, 17:845-858.
89. Jacobson S.G., Aleman T.S., Cideciyan A.V., Heon E., Golczak M., Beltran W.A., Sumaroka A., Schwartz S.B., Roman A.J., Windsor E.A., et al. Human cone photoreceptor dependence on RPE65 isomerase. Proc. Natl. Acad. Sci. U. S. A. 2007, 104:15123-15128.
90. Jacobson S.G., Cideciyan A.V., Aleman T.S., Sumaroka A., Schwartz S.B., Windsor E.A., Roman A.J., Heon E., Stone E.M., Thompson D.A. RDH12 and RPE65, visual cycle genes causing leber congenital amaurosis, differ in disease expression. Investig. Ophthalmol. Vis. Sci. 2007, 48:332-338.
91. Jacobson S.G., Cideciyan A.V., Aleman T.S., Sumaroka A., Windsor E.A., Schwartz S.B., Heon E., Stone E.M. Photoreceptor layer topography in children with leber congenital amaurosis caused by RPE65 mutations. Investig. Ophthalmol. Vis. Sci. 2008, 49:4573-4577.
92. Jacobson S.G., Cideciyan A.V., Aleman T.S., Sumaroka A., Roman A.J., Gardner L.M., Prosser H.M., Mishra M., Bech-Hansen N.T., Herrera W., et al. Usher syndromes due to MYO7A, PCDH15, USH2A or GPR98 mutations share retinal disease mechanism. Hum. Mol. Genet. 2008, 17:2405-2415.
93. Jacobson S.G., Aleman T.S., Cideciyan A.V., Roman A.J., Sumaroka A., Windsor E.A., Schwartz S.B., Heon E., Stone E.M. Defining the residual vision in leber congenital amaurosis caused by RPE65 mutations. Investig. Ophthalmol. Vis. Sci. 2009, 50:2368-2375.
94. Jeon C.J., Strettoi E., Masland R.H. The major cell populations of the mouse retina. J. Neurosci. 1998, 18:8936-8946.
95. Jin M., Li S., Moghrabi W.N., Sun H., Travis G.H. Rpe65 is the retinoid isomerase in bovine retinal pigment epithelium. Cell 2005, 122:449-459.
96. Katz M.L., White H.A., Gao C.L., Roth G.S., Knapka J.J., Ingram D.K. Dietary restriction slows age pigment accumulation in the retinal pigment epithelium. Investig. Ophthalmol. Vis. Sci. 1993, 34:3297-3302.
97. Katz M.L., Gao C.L., Rice L.M. Long-term variations in cyclic light intensity and dietary vitamin A intake modulate lipofuscin content of the retinal pigment epithelium. J. Neurosci. Res. 1999, 57:106-116.
98. Katz M.L., Redmond T.M. Effect of Rpe65 knockout on accumulation of lipofuscin fluorophores in the retinal pigment epithelium. Investig. Ophthalmol. Vis. Sci. 2001, 42:3023-3030.
99. Kijas J.W., Cideciyan A.V., Aleman T.S., Pianta M.J., Pearce-Kelling S.E., Miller B.J., Jacobson S.G., Aguirre G.D., Acland G.M. Naturally occurring rhodopsin mutation in the dog causes retinal dysfunction and degeneration mimicking human dominant retinitis pigmentosa. Proc. Natl. Acad. Sci. U. S. A. 2002, 99:6328-6333.
100. Kiser P.D., Golczak M., Lodowski D.T., Chance M.R., Palczewski K. Crystal structure of native RPE65, the retinoid isomerase of the visual cycle. Proc. Natl. Acad. Sci. U. S. A. 2009, 106:17325-17330.
101. Kleim J.A., Chan S., Pringle E., Schallert K., Procaccio V., Jimenez R., Cramer S.C. BDNF val66met polymorphism is associated with modified experience-dependent plasticity in human motor cortex. Nat. Neurosci. 2006, 9:735-737.
102. Koenekoop R.K. Leber congenital amaurosis. Retinal Degenerations: Biology, Diagnostics, and Therapeutics 2007, 61-90. Humana Press, New Jersey. J. Tombran-Tink, C.J. Barnstable (Eds.).
103. Komáromy, A.M., Alexander, J.J., Rowlan, J.S., Garcia, M.M., Chiodo, V.A., Kaya, A., Tanaka, J.C., Acland, G.M., Hauswirth, W.W., Aguirre, G.D., 2010. Gene therapy rescues cone function in congenital achromatopsia. Hum. Mol. Genet., in press.
104. Kral A., Tillein J., Heid S., Klinke R., Hartmann R. Cochlear implants: cortical plasticity in congenital deprivation. Prog. Brain Res. 2006, 157:283-313.
105. Kroll A.J., Kuwabara T. Electron microscopy of a retinal abiotrophy. Arch. Ophthalmol. 1964, 71:683-690.
106. Kunchithapautham K., Coughlin B., Crouch R.K., Rohrer B. Cone outer segment morphology and cone function in the Rpe65-/- Nrl-/- mouse retina are amenable to retinoid replacement. Investig. Ophthalmol. Vis. Sci. 2009, 50:4858-4864.
107. Lai C.M., Yu M.J., Brankov M., Barnett N.L., Zhou X., Redmond T.M., Narfstrom K., Rakoczy P.E. Recombinant adeno-associated virus type 2-mediated gene delivery into the Rpe65-/- knockout mouse eye results in limited rescue. Genet. Vaccines Ther 2004, 2:3.
108. Lamb T.D., Pugh E.N. Dark adaptation and the retinoid cycle of vision. Prog. Retin. Eye Res. 2004, 23:307-380.
109. Lambert S.R., Taylor D., Kriss A. The infant with nystagmus, normal appearing fundi, but an abnormal ERG. Surv. Ophthalmol. 1989, 34:173-186.
110. Le Meur G., Stieger K., Smith A.J., Weber M., Deschamps J.Y., Nivard D., Mendes-Madeira A., Provost N., Péréon Y., Cherel Y., et al. Restoration of vision in RPE65-deficient Briard dogs using an AAV serotype 4 vector that specifically targets the retinal pigmented epithelium. Gene Ther. 2007, 14:292-303.
111. Lei H., Schuchard R.A. Using two preferred retinal loci for different lighting conditions in patients with central scotomas. Investig. Ophthalmol. Vis. Sci. 1997, 38:1812-1818.
112. Leigh R.J., Zee D.S. Eye movements of the blind. Investig. Ophthalmol. Vis. Sci. 1980, 19:328-331.
113. Levi D.M., Li R.W. Improving the performance of the amblyopic visual system. Philos. Trans. R. Soc. Lond. B. Biol. Sci. 2009, 364:399-407.
114. Levin N., Dumoulin S.O., Winawer J., Dougherty R.F., Wandell B.A. Cortical maps and white matter tracts following long period of visual deprivation and retinal image restoration. Neuron 2010, 65:21-31.
115. Li W., Kong F., Li X., Dai X., Liu X., Zheng Q., Wu R., Zhou X., Lü F., Chang B., et al. Gene therapy following subretinal AAV5 vector delivery is not affected by a previous intravitreal AAV5 vector administration in the partner eye. Mol. Vis. 2009, 15:267-275.
116. Little D.M., Thulborn K.R., Szlyk J.P. An FMRI study of saccadic and smooth-pursuit eye movement control in patients with age-related macular degeneration. Investig. Ophthalmol. Vis. Sci. 2008, 49:1728-1735.
117. Loewenfeld I.E. The light reflex. The Pupil: Anatomy, Physiology and Clinical Applications 1993, 193-267. Iowa State University Press, Ames, Iowa. I.E. Loewenfeld (Ed.).
118. Lorenz B., Gyürüs P., Preising M., Bremser D., Gu S., Andrassi M., Gerth C., Gal A. Early-onset severe rod-cone dystrophy in young children with RPE65 mutations. Investig. Ophthalmol. Vis. Sci. 2000, 41:2735-2742.
119. Lorenz B., Wabbels B., Wegscheider E., Hamel C.P., Drexler W., Preising M.N. Lack of fundus autofluorescence to 488 nanometers from childhood on in patients with early-onset severe retinal dystrophy associated with mutations in RPE65. Ophthalmology 2004, 111:1585-1594.
120. Lorenz B., Poliakov E., Schambeck M., Friedburg C., Preising M.N., Redmond T.M. A comprehensive clinical and biochemical functional study of a novel RPE65 hypomorphic mutation. Investig. Ophthalmol. Vis. Sci. 2008, 49:5235-5242.
121. Lotery A.J., Namperumalsamy P., Jacobson S.G., Weleber R.G., Fishman G.A., Musarella M.A., Hoyt C.S., Héon E., Levin A., Jan J., et al. Mutation analysis of 3 genes in patients with Leber congenital amaurosis. Arch. Ophthalmol. 2000, 118:538-543.
122. Lucas R.J., Hattar S., Takao M., Berson D.M., Foster R.G., Yau K.W. Diminished pupillary light reflex at high irradiances in melanopsin knockout mice. Science 2003, 299:245-247.
123. Lyubarsky A.L., Falsini B., Pennesi M.E., Valentini P., Pugh E.N. UV- and midwave-sensitive cone-driven retinal responses of the mouse: a possible phenotype for coexpression of cone photopigments. J. Neurosci. 1999, 19:442-455.
124. Lyubarsky A.L., Savchenko A.B., Morocco S.B., Daniele L.L., Redmond T.M., Pugh E.N. Mole quantity of RPE65 and its productivity in the generation of 11-cis-retinal from retinyl esters in the living mouse eye. Biochemistry 2005, 44:9880-9888.
125. Machida S., Kondo M., Jamison J.A., Khan N.W., Kononen L.T., Sugawara T., Bush R.A., Sieving P.A. P23H rhodopsin transgenic rat: correlation of retinal function with histopathology. Investig. Ophthalmol. Vis. Sci. 2000, 41:3200-3209.
126. Maeda T., Cideciyan A.V., Maeda A., Golczak M., Aleman T.S., Jacobson S.G., Palczewski K. Loss of cone photoreceptors caused by chromophore depletion is partially prevented by the artificial chromophore pro-drug, 9-cis-retinyl acetate. Hum. Mol. Genet. 2009, 18:2277-2287.
127. Maeda, A., Okano, K., Park, P.S., Lem, J., Crouch, R.K., Maeda, T., Palczewski, K. Palmitoylation stabilizes unliganded rod opsin. Proc. Natl. Acad. Sci. U S A., in press.
128. Maguire A.M., Simonelli F., Pierce E.A., Pugh E.N., Mingozzi F., Bennicelli J., Banfi S., Marshall K.A., Testa F., Surace E.M., et al. Safety and efficacy of gene transfer for Leber's congenital amaurosis. N. Engl. J. Med. 2008, 358:2240-2248.
129. Maguire A.M., High K.A., Auricchio A., Wright J.F., Pierce E.A., Testa F., Mingozzi F., Bennicelli J.L., Ying G.S., Rossi S., 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.
130. Mamatha G., Srilekha S., Meenakshi S., Kumaramanickavel G. Screening of the RPE65 gene in the Asian Indian patients with Leber congenital amaurosis. Ophthalmic Genet. 2008, 29:73-78.
131. Marlhens F., Bareil C., Griffoin J.M., Zrenner E., Amalric P., Eliaou C., Liu S.Y., Harris E., Redmond T.M., Arnaud B., et al. Mutations in RPE65 cause Leber's congenital amaurosis. Nat. Genet. 1997, 17:139-141.
132. Marlhens F., Griffoin J.M., Bareil C., Arnaud B., Claustres M., Hamel C.P. Autosomal recessive retinal dystrophy associated with two novel mutations in the RPE65 gene. Eur. J. Hum. Genet. 1998, 6:527-531.
133. Mata N.L., Weng J., Travis G.H. Biosynthesis of a major lipofuscin fluorophore in mice and humans with ABCR-mediated retinal and macular degeneration. Proc. Natl. Acad. Sci. U. S. A. 2000, 97:7154-7159.
134. Maurer D., Ellemberg D., Lewis T.L. Repeated measurements of contrast sensitivity reveal limits to visual plasticity after early binocular deprivation in humans. Neuropsychologia 2006, 44:2104-2112.
135. McBee J.K., Palczewski K., Baehr W., Pepperberg D.R. Confronting complexity: the interlink of phototransduction and retinoid metabolism in the vertebrate retina. Prog. Retin. Eye Res. 2001, 20:469-529.
136. McCloskey M. Spatial representations and multiple-visual-systems hypotheses: evidence from a developmental deficit in visual location and orientation processing. Cortex 2004, 40:677-694.
137. Mechler F., Victor J.D., Purpura K.P., Shapley R. Robust temporal coding of contrast by V1 neurons for transient but not for steady-state stimuli. J. Neurosci. 1998, 18:6583-6598.
138. Miller J.W. Preliminary results of gene therapy for retinal degeneration. N. Engl. J. Med. 2008, 358:2282-2284.
139. Milner A.D., Goodale M.A. Two visual systems reviewed. Neuropsychologia 2008, 46:774-785.
140. Mizuno K., Takei Y., Sears M.L., Peterson W.S., Carr R.E., Jampol L.M. Leber's congenital amaurosis. Am. J. Ophthalmol. 1977, 83:32-42.
141. Moise A.R., Noy N., Palczewski K., Blaner W.S. Delivery of retinoid-based therapies to target tissues. Biochemistry 2007, 46:4449-4458.
142. Moiseyev G., Chen Y., Takahashi Y., Wu B.X., Ma J.X. Rpe65 is the isomerohydrolase in the retinoid visual cycle. Proc. Natl. Acad. Sci. U. S. A. 2005, 102:12413-12418.
143. Moradi P., Moore A.T. Molecular genetics of infantile-onset retinal dystrophies. Eye (Lond) 2007, 21:1344-1351.
144. Morimura H., Fishman G.A., Grover S.A., Fulton A.B., Berson E.L., Dryja T.P. Mutations in the RPE65 gene in patients with autosomal recessive retinitis pigmentosa or leber congenital amaurosis. Proc. Natl. Acad. Sci. U. S. A. 1998, 95:3088-3093.
145. Narfström K., Wrigstad A., Nilsson S.E. The Briard dog: a new animal model of congenital stationary night blindness. Br. J. Ophthalmol. 1989, 73:750-756.
146. Narfström K., Katz M.L., Bragadottir R., Seeliger M., Boulanger A., Redmond T.M., Caro L., Lai C.M., Rakoczy P.E. Functional and structural recovery of the retina after gene therapy in the RPE65 null mutation dog. Investig. Ophthalmol. Vis. Sci. 2003, 44:1663-1672.
147. Narfström K., VaeganKatz M., Bragadottir R., Rakoczy E.P., Seeliger M. Assessment of structure and function over a 3-year period after gene transfer in RPE65-/- dogs. Doc. Ophthalmol. 2005, 111:39-48.
148. Narfström K., Tullis G.E., Seeliger M. Effective treatment for the canine RPE65 null mutation, a hereditary retinal dystrophy comparable to human Leber's congenital amaurosis. Retinal Degenerations: Biology, Diagnostics, and Therapeutics 2007, 415-431. Humana Press, New Jersey. J. Tombran-Tink, C.J. Barnstable (Eds.).
149. Narfström K., Seeliger M., Lai C.M., VaeganKatz M., Rakoczy E.P., Remé C. Morphological aspects related to long-term functional improvement of the retina in the 4 years following rAAV-mediated gene transfer in the RPE65 null mutation dog. Adv. Exp. Med. Biol. 2008, 613:139-146.
150. Nikolaeva O., Takahashi Y., Moiseyev G., Ma J.X. Negative charge of the glutamic acid 417 residue is crucial for isomerohydrolase activity of RPE65. Biochem. Biophys. Res. Commun 2010, 391:1757-1761.
151. Nilsson S.E., Wrigstad A., Narfström K. Changes in the DC electroretinogram in Briard dogs with hereditary congenital night blindness and partial day blindness. Exp. Eye Res. 1992, 54:291-296.
152. Noble K.G., Carr R.E. Leber's congenital amaurosis. Arch. Ophthalmol. 1978, 96:818-821.
153. Noppeney U., Friston K.J., Ashburner J., Frackowiak R., Price C.J. Early visual deprivation induces structural plasticity in gray and white matter. Curr. Biol. 2005, 15:R488-R490.
154. Nusinowitz S., Ridder W.H., Pang J.J., Chang B., Noorwez S.M., Kaushal S., Hauswirth W.W., Heckenlively J.R. Cortical visual function in the rd12 mouse model of Leber Congenital Amarousis (LCA) after gene replacement therapy to restore retinal function. Vision Res. 2006, 46:3926-3934.
155. Pang J.J., Chang B., Hawes N.L., Hurd R.E., Davisson M.T., Li J., Noorwez S.M., Malhotra R., McDowell J.H., Kaushal S., et al. Retinal degeneration 12 (rd12): a new, spontaneously arising mouse model for human Leber congenital amaurosis (LCA). Mol. Vis. 2005, 11:152-162.
156. Pang J.J., Chang B., Kumar A., Nusinowitz S., Noorwez S.M., Li J., Rani A., Foster T.C., Chiodo V.A., Doyle T., et al. Gene therapy restores vision-dependent behavior as well as retinal structure and function in a mouse model of RPE65 Leber congenital amaurosis. Mol. Ther. 2006, 13:565-572.
157. Pang, J., Boye, S.E., Lei, B., Boye, S.L., Everhart, D., Ryals, R., Umino, Y., Rohrer, B., Alexander, J., Li, J., et al. Self-complementary AAV-mediated gene therapy restores cone function and prevents cone degeneration in two models of Rpe65 deficiency. Gene Ther., in press.
158. Parish C.A., Hashimoto M., Nakanishi K., Dillon J., Sparrow J. Isolation and one-step preparation of A2E and iso-A2E, fluorophores from human retinal pigment epithelium. Proc. Natl. Acad. Sci. U. S. A. 1998, 95:14609-14613.
159. Pasadhika, S., Fishman, G.A., Stone, E.M., Lindeman, M., Zelkha, R., Lopez, I., Koenekoop, R.K., Shahidi, M. Differential macular morphology in patients with RPE65, CEP290, GUCY2D and AIPL1 related Leber congenital amaurosis. Invest. Ophthalmol. Vis. Sci., in press.
160. Paunescu K., Wabbels B., Preising M.N., Lorenz B. Longitudinal and cross-sectional study of patients with early-onset severe retinal dystrophy associated with RPE65 mutations. Graefes Arch. Clin. Exp. Ophthalmol. 2005, 243:417-426.
161. Perrault I., Rozet J.M., Ghazi I., Leowski C., Bonnemaison M., Gerber S., Ducroq D., Cabot A., Souied E., Dufier J.L., et al. Different functional outcome of RetGC1 and RPE65 gene mutations in Leber congenital amaurosis. Am. J. Hum. Genet. 1999, 64:1225-1228.
162. Philp A.R., Jin M., Li S., Schindler E.I., Iannaccone A., Lam B.L., Weleber R.G., Fishman G.A., Jacobson S.G., Mullins R.F., et al. Predicting the pathogenicity of RPE65 mutations. Hum. Mutat. 2009, 30:1183-1188.
163. Poehner W.J., Fossarello M., Rapoport A.L., Aleman T.S., Cideciyan A.V., Jacobson S.G., Wright A.F., Danciger M., Farber D.B. A homozygous deletion in RPE65 in a small Sardinian family with autosomal recessive retinal dystrophy. Mol. Vis. 2000, 6:192-198.
164. Porto F.B., Perrault I., Hicks D., Rozet J.M., Hanoteau N., Hanein S., Kaplan J., Sahel J.A. Prenatal human ocular degeneration occurs in Leber's congenital amaurosis (LCA2). J. Gene Med. 2002, 4:390-396.
165. Porto F.B., Perrault I., Hicks D., Rozet J.M., Hanoteau N., Hanein S., Kaplan J., Sahel J.A. Prenatal human ocular degeneration occurs in Leber's congenital amaurosis (LCA1 and 2). Adv. Exp. Med. Biol. 2003, 533:59-68.
166. Puliafito C.A., Fujimoto J.G., Schuman J.S., Hee M.R. Optical Coherence Tomography of Ocular Diseases 1996, Slack Inc., Thorofare, New Jersey.
167. Rangaswamy, N.V., Patel, H.M., Locke, K.G., Hood, D.C., Birch, D.G. A comparison of visual field sensitivity to photoreceptor thickness in retinitis pigmentosa. Invest. Ophthalmol. Vis. Sci., in press.
168. Rando R.R. The biochemistry of the visual cycle. Chem. Rev. 2001, 101:1881-1896.
169. Redmond T.M. Focus on molecules: RPE65, the visual cycle retinol isomerase. Exp. Eye Res. 2009, 88:846-847.
170. Redmond T.M., Yu S., Lee E., Bok D., Hamasaki D., Chen N., Goletz P., Ma J.X., Crouch R.K., Pfeifer K. Rpe65 is necessary for production of 11-cis-vitamin A in the retinal visual cycle. Nat. Genet. 1998, 20:344-351.
171. Redmond T.M., Poliakov E., Yu S., Tsai J.Y., Lu Z., Gentleman S. 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.
172. Redmond T.M., Poliakov E., Kuo S., Chander P., Gentleman S. RPE65, visual cycle retinol isomerase, is not inherently 11-cis-specific: support for a carbocation mechanism of retinol isomerization. J. Biol. Chem. 2010, 285:1919-1927.
173. Rex T.S. Rescue of sight by gene therapy - closer than it may appear. Ophthalmic Genet. 2007, 28:127-133.
174. Riis R.C., Aguirre G.D. The briard problem. Proc. Am. Coll. Vet. Ophthalmol. 1983, 62-75.
175. Rohrer B., Goletz P., Znoiko S., Ablonczy Z., Ma J.X., Redmond T.M., Crouch R.K. Correlation of regenerable opsin with rod ERG signal in Rpe65-/- mice during development and aging. Investig. Ophthalmol. Vis. Sci. 2003, 44:310-315.
176. Rohrer B., Lohr H.R., Humphries P., Redmond T.M., Seeliger M.W., Crouch R.K. Cone opsin mislocalization in Rpe65-/- mice: a defect that can be corrected by 11-cis retinal. Investig. Ophthalmol. Vis. Sci. 2005, 46:3876-3882.
177. Roman A.J., Schwartz S.B., Aleman T.S., Cideciyan A.V., Chico J.D., Windsor E.A., Gardner L.M., Ying G.S., Smilko E.E., Maguire M.G., et al. Quantifying rod photoreceptor-mediated vision in retinal degenerations: dark-adapted thresholds as outcome measures. Exp. Eye Res. 2005, 80:259-272.
178. Roman A.J., Cideciyan A.V., Aleman T.S., Jacobson S.G. Full-field stimulus testing (FST) to quantify visual perception in severely blind candidates for treatment trials. Physiol. Meas. 2007, 28:N51-N56.
179. Roman A.J., Boye S.L., Aleman T.S., Pang J.J., McDowell J.H., Boye S.E., Cideciyan A.V., Jacobson S.G., Hauswirth W.W. Electroretinographic analyses of Rpe65-mutant rd12 mice: developing an in vivo bioassay for human gene therapy trials of Leber congenital amaurosis. Mol. Vis. 2007, 13:1701-1710.
180. Samardzija M., von Lintig J., Tanimoto N., Oberhauser V., Thiersch M., Remé C.E., Seeliger M., Grimm C., Wenzel A. R91W mutation in Rpe65 leads to milder early-onset retinal dystrophy due to the generation of low levels of 11-cis-retinal. Hum. Mol. Genet. 2008, 17:281-292.
181. Samardzija M., Tanimoto N., Kostic C., Beck S., Oberhauser V., Joly S., Thiersch M., Fahl E., Arsenijevic Y., von Lintig J., 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.
182. Sasaki Y., Nanez J.E., Watanabe T. Advances in visual perceptual learning and plasticity. Nat. Rev. Neurosci. 2010, 11:53-60.
183. Schweitzer N.M., Bouman M.A. Differential threshold measurements on the light reflex of the human pupil. A.M.A. Arch. Ophthalmol. 1958, 59:541-550.
184. Seeliger M.W., Grimm C., Ståhlberg F., Friedburg C., Jaissle G., Zrenner E., Guo H., Remé C.E., Humphries P., Hofmann 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.
185. Shimony J.S., Burton H., Epstein A.A., McLaren D.G., Sun S.W., Snyder A.Z. Diffusion tensor imaging reveals white matter reorganization in early blind humans. Cereb. Cortex 2006, 16:1653-1661.
186. Shlaer S., Smith E.L., Chase A.M. Visual acuity and illumination in different spectral regions. J. Gen. Physiol. 1942, 25:553-569.
187. Simonelli F., Ziviello C., Testa F., Rossi S., Fazzi E., Bianchi P.E., Fossarello M., Signorini S., Bertone C., Galantuomo S., et al. Clinical and molecular genetics of Leber's congenital amaurosis: a multicenter study of Italian patients. Investig. Ophthalmol. Vis. Sci. 2007, 48:4284-4290.
188. Simonelli F., Maguire A.M., Testa F., Pierce E.A., Mingozzi F., Bennicelli J.L., Rossi S., Marshall K., Banfi S., Surace E.M., et al. Gene therapy for Leber's congenital amaurosis is safe and effective through 1.5 years after vector administration. Mol. Ther 2010, 18:643-650.
189. Sjöstrand, J., Magnusson, G., Nyström, A., Jonsson, R. Stability of visual outcome from 7 years in children treated surgically for bilateral dense congenital cataracts before 37 weeks of age. Acta Ophthalmol., in press.
190. Smirnakis S.M., Brewer A.A., Schmid M.C., Tolias A.S., Schüz A., Augath M., Inhoffen W., Wandell B.A., Logothetis N.K. Lack of long-term cortical reorganization after macaque retinal lesions. Nature 2005, 435:300-307.
191. Smith A.J., Bainbridge J.W., Ali R.R. Prospects for retinal gene replacement therapy. Trends Genet. 2009, 25:156-165.
192. Stone E.M. Leber congenital amaurosis-a model for efficient genetic testing of heterogeneous disorders: LXIV Edward Jackson Memorial Lecture. Am. J. Ophthalmol. 2007, 144:791-811.
193. Stone E.M. Progress toward effective treatments for human photoreceptor degenerations. Curr. Opin. Genet. Dev. 2009, 19:283-289.
194. Sunness J.S., Liu T., Yantis S. Retinotopic mapping of the visual cortex using functional magnetic resonance imaging in a patient with central scotomas from atrophic macular degeneration. Ophthalmology 2004, 111:1595-1598.
195. Takahashi Y., Chen Y., Moiseyev G., Ma J.X. Two point mutations of RPE65 from patients with retinal dystrophies decrease the stability of RPE65 protein and abolish its isomerohydrolase activity. J. Biol. Chem. 2006, 281:21820-21826.
196. Thomson H., Lotery A. The promise of nanomedicine for ocular disease. Nanomed 2009, 4:599-604.
197. Thompson D.A., Gyürüs P., Fleischer L.L., Bingham E.L., McHenry C.L., Apfelstedt-Sylla E., Zrenner E., Lorenz B., Richards J.E., Jacobson S.G., et al. Genetics and phenotypes of RPE65 mutations in inherited retinal degeneration. Investig. Ophthalmol. Vis. Sci. 2000, 41:4293-4299.
198. Thompson D.A., McHenry C.L., Li Y., Richards J.E., Othman M.I., Schwinger E., Vollrath D., Jacobson S.G., Gal A. Retinal dystrophy due to paternal isodisomy for chromosome 1 or chromosome 2, with homoallelism for mutations in RPE65 or MERTK, respectively. Am. J. Hum. Genet. 2002, 70:224-229.
199. Thompson S., Mullins R.F., Philp A.R., Stone E.M., Mrosovsky N. Divergent phenotypes of vision and accessory visual function in mice with visual cycle dysfunction (Rpe65 rd12) or retinal degeneration (rd/rd). Investig. Ophthalmol. Vis. Sci. 2008, 49:2737-2742.
200. Travis G.H., Golczak M., Moise A.R., Palczewski K. Diseases caused by defects in the visual cycle: retinoids as potential therapeutic agents. Annu. Rev. Pharmacol. Toxicol. 2007, 47:469-512.
201. Tu D.C., Owens L.A., Anderson L., Golczak M., Doyle S.E., McCall M., Menaker M., Palczewski K., Van Gelder R.N. Inner retinal photoreception independent of the visual retinoid cycle. Proc. Natl. Acad. Sci. U. S. A. 2006, 103:10426-10431.
202. Van Hooser J.P., Aleman T.S., He Y.G., Cideciyan A.V., Kuksa V., Pittler S.J., Stone E.M., Jacobson S.G., Palczewski K. Rapid restoration of visual pigment and function with oral retinoid in a mouse model of childhood blindness. Proc. Natl. Acad. Sci. U. S. A. 2000, 97:8623-8628.
203. Van Hooser J.P., Liang Y., Maeda T., Kuksa V., Jang G.F., He Y.G., Rieke F., Fong H.K., Detwiler P.B., Palczewski K. Recovery of visual functions in a mouse model of Leber congenital amaurosis. J. Biol. Chem. 2002, 277:19173-19182.
204. Veske A., Nilsson S.E., Narfström K., Gal A. Retinal dystrophy of Swedish briard/briard-beagle dogs is due to a 4-bp deletion in RPE65. Genomics 1999, 57:57-61.
205. Volpe N.J., Dadvand L., Kim S.K., Maguire M.G., Ying G.S., Moster M.L., Galetta S.L. Computerized binocular pupillography of the swinging flashlight test detects afferent pupillary defects. Curr. Eye Res. 2009, 34:606-613.
206. von Rückmann A., Fitzke F.W., Bird A.C. Distribution of fundus autofluorescence with a scanning laser ophthalmoscope. Br. J. Ophthalmol. 1995, 79:407-412.
207. Wabbels B., Demmler A., Paunescu K., Wegscheider E., Preising M.N., Lorenz B. Fundus autofluorescence in children and teenagers with hereditary retinal diseases. Graefes Arch. Clin. Exp. Ophthalmol. 2006, 244:36-45.
208. Walia, S., Fishman, G.A., Jacobson, S.G., Aleman, T.S., Koenekoop, R.K., Traboulsi, E.I., Weleber, R.G., Pennesi, M.E., Heon, E., Drack, A., et al. Visual acuity in patients with Leber's congenital amaurosis and early childhood-onset retinitis pigmentosa. Ophthalmology, in press.
209. Wang J.S., Kefalov V.J. An alternative pathway mediates the mouse and human cone visual cycle. Curr. Biol. 2009, 19:1665-1669.
210. Wassell J., Boulton M. A role for vitamin A in the formation of ocular lipofuscin. Br. J. Ophthalmol. 1997, 81:911-918.
211. Wenzel A., Reme C.E., Williams T.P., Hafezi F., Grimm C. The Rpe65 Leu450Met variation increases retinal resistance against light-induced degeneration by slowing rhodopsin regeneration. J. Neurosci. 2001, 21:53-58.
212. Wenzel A., von Lintig J., Oberhauser V., Tanimoto N., Grimm C., Seeliger M.W. RPE65 is essential for the function of cone photoreceptors in NRL-deficient mice. Investig. Ophthalmol. Vis. Sci. 2007, 48:534-542.
213. Wilhelm H. The pupil. Curr. Opin. Neurol. 2008, 21:36-42.
214. Woodruff M.L., Wang Z., Chung H.Y., Redmond T.M., Fain G.L., Lem J. Spontaneous activity of opsin apoprotein is a cause of Leber congenital amaurosis. Nat. Genet. 2003, 35:158-164.
215. Wright A.F., Jacobson S.G., Cideciyan A.V., Roman A.J., Shu X., Vlachantoni D., McInnes R.R., Riemersma R.A. Lifespan and mitochondrial control of neurodegeneration. Nat. Genet. 2004, 36:153-158.
216. Wright A.F., Chakarova C.F., Abd El-Aziz M.M., Bhattacharya S.S. Photoreceptor degeneration: genetic and mechanistic dissection of a complex trait. Nat. Rev. Genet. 2010, 11:273-284.
217. Wrigstad A., Nilsson S.E., Narfström K. Ultrastructural changes of the retina and the retinal pigment epithelium in Briard dogs with hereditary congenital night blindness and partial day blindness. Exp. Eye Res. 1992, 55:805-818.
218. Wrigstad A., Narfström K., Nilsson S.E. Slowly progressive changes of the retina and retinal pigment epithelium in Briard dogs with hereditary retinal dystrophy. A morphological study. Doc. Ophthalmol. 1994, 87:337-354.
219. Yamahachi H., Marik S.A., McManus J.N., Denk W., Gilbert C.D. Rapid axonal sprouting and pruning accompany functional reorganization in primary visual cortex. Neuron 2009, 64:719-729.
220. Yáñez-Muñoz R.J., Balaggan K.S., MacNeil A., Howe S.J., Schmidt M., Smith A.J., Buch P., MacLaren R.E., Anderson P.N., Barker S.E., et al. Effective gene therapy with nonintegrating lentiviral vectors. Nat. Med. 2006, 12:348-353.
221. Yzer S., van den Born L.I., Schuil J., Kroes H.Y., van Genderen M.M., Boonstra F.N., van den Helm B., Brunner H.G., Koenekoop R.K., Cremers F.P. A Tyr368His RPE65 founder mutation is associated with variable expression and progression of early onset retinal dystrophy in 10 families of a genetically isolated population. J. Med. Genet. 2003, 40:709-713.
222. Zhang H., Fan J., Li S., Karan S., Rohrer B., Palczewski K., Frederick J.M., Crouch R.K., Baehr W. Trafficking of membrane-associated proteins to cone photoreceptor outer segments requires the chromophore 11-cis-retinal. J. Neurosci. 2008, 28:4008-4014.
223. Znoiko S.L., Crouch R.K., Moiseyev G., Ma J.X. Identification of the RPE65 protein in mammalian cone photoreceptors. Investig. Ophthalmol. Vis. Sci. 2002, 43:1604-1609.
224. Znoiko S.L., Rohrer B., Lu K., Lohr H.R., Crouch R.K., Ma J.X. Downregulation of cone-specific gene expression and degeneration of cone photoreceptors in the Rpe65-/- mouse at early ages. Investig. Ophthalmol. Vis. Sci. 2005, 46:1473-1479.