Lighting a candle in the dark: advances in genetics and gene therapy of recessive retinal dystrophies.
Nonsyndromic recessive retinal dystrophies cause severe visual impairment due to the death of photoreceptor and retinal pigment epithelium cells. These diseases until recently have been considered to be incurable. Molecular genetic studies in the last two decades have revealed the underlying molecular causes in approximately two-thirds of patients. The mammalian eye has been at the forefront of therapeutic trials based on gene augmentation in humans with an early-onset nonsyndromic recessive retinal dystrophy due to mutations in the retinal pigment epithelium-specific protein 65kDa (RPE65) gene. Tremendous challenges still lie ahead to extrapolate these studies to other retinal disease-causing genes, as human gene augmentation studies require testing in animal models for each individual gene and sufficiently large patient cohorts for clinical trials remain to be identified through cost-effective mutation screening protocols.
den Hollander
Anneke I
AI
Department of Ophthalmology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands.
Black
Aaron
A
Bennett
Jean
J
Cremers
Frans P M
FP
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics; D002415:Cats; D004195:Disease Models, Animal; D004285:Dogs; D005123:Eye / Q000033:anatomy & histology / Q000473:pathology; D005136:Eye Proteins / Q000235:genetics; D018014:Gene Transfer Techniques; D005796:Genes; D005808:Genes, Recessive; D005820:Genetic Testing; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008029:Lighting; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D012160:Retina / Q000378:metabolism; D012164:Retinal Diseases / Q000235:genetics* / Q000378:metabolism* / Q000628:therapy; D012172:Retinaldehyde / Q000235:genetics; D019076:Transgenes; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase
D002352:Carrier Proteins; D005136:Eye Proteins; D012172:Retinaldehyde; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase
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