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[Essentials in Ophthalmology] Advances in Vision Research, Volume II (Genetic Eye Research in Asia and the Pacific) || Genetics and Susceptibility of Retinal Eye Diseases in India
摘要： As per the World Health Organization, genetic eye disorders are one of the top ten major causes of global ocular health burden. AMD and DR take major share of the adult eye diseases component that particularly affects the neurovascular retina. More than 100 genes are known to cause Mendelian types of retinal degenerations including syndromic and non-syndromic RP, and it is presumed that this constitutes only 60% of all the genes known so far, and the remaining are yet to be identified. The burden of genetic disorders in India is significant, and very many significant genes like RPE65 have been identified with consanguineous autosomal recessive pedigrees obtained from this region.
关键词： Visual cycle,Phototransduction pathway,Stargardt disease,Retinitis pigmentosa,Leber congenital amaurosis
更新于2025-09-23 15:21:21
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Effect of an intravitreal antisense oligonucleotide on vision in Leber congenital amaurosis due to a photoreceptor cilium defect
摘要： Photoreceptor ciliopathies constitute the most common molecular mechanism of the childhood blindness Leber congenital amaurosis. Ten patients with Leber congenital amaurosis carrying the c.2991+1655A>G allele in the ciliopathy gene centrosomal protein 290 (CEP290) were treated (ClinicalTrials.gov no. NCT03140969) with intravitreal injections of an antisense oligonucleotide to restore correct splicing. There were no serious adverse events, and vision improved at 3?months. The visual acuity of one exceptional responder improved from light perception to 20/400.
关键词： antisense oligonucleotide,CEP290,photoreceptor ciliopathies,Leber congenital amaurosis,vision improvement
更新于2025-09-09 09:28:46
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Concepts and Strategies in Retinal Gene Therapy
摘要： Genetic defects of the retina or retinal pigment epithelium (RPE) cause a substantial number of sight-impairing or blinding disorders, many of which eventually cause the degeneration and death of the visual cells. Previously considered incurable, some of these retinal diseases can now be treated, at least experimentally, by gene therapy. This new era of retinal therapeutics followed the successful restoration of retinal function in a canine model of RPE65 Leber congenital amaurosis (LCA) through adeno-associated virus 2 (AAV2) vector-mediated gene augmentation targeting the RPE layer of the eye. Restoring isomerohydrolase activity in the RPE corrected the retinoid visual cycle and vision defect. When treated at the predegenerate disease stage, treatment was both effective and permanent, and photoreceptor structure was preserved. Validation studies by other groups in both large and small animal models, along with preclinical safety studies in nonhuman primates (NPHs) and dogs, confirmed that the treatment was safe and effective. A further series of detailed studies in patients and animal models established the dependence of human cone photoreceptors on RPE65 isomerase, determined that the remaining photoreceptors in blind eyes were amenable to treatment, showed that the visual cortex in man and dog was intact and responsive in spite of early blindness, and developed outcome measures that could be used readily to assess treatment outcomes. These studies were followed by three independent clinical trials showing the treatment to be safe. Since then, additional RPE65-LCA clinical trials have been initiated both in academic settings and through commercial entities in the United States and elsewhere. To date, LCA remains the only blinding genetic disease to be successfully treated in humans.
关键词： RPE65,AAV vectors,photoreceptor degeneration,Leber congenital amaurosis,retinal gene therapy
更新于2025-09-04 15:30:14