title: Leber's congenital amaurosis and the role of gene therapy in congenital retinal disorders.
abstract: Leber's congenital amaurosis (LCA) and recent gene therapy advancement for treating inherited retinopathies were extensive literature reviewed using MEDLINE, PubMed and EMBASE. Adeno-associated viral vectors were the most utilised vectors for ocular gene therapy. Cone photoreceptor cells might use an alternate pathway which was not reliant of the retinal pigment epithelium (RPE) derived retinoid isomerohydrolase (RPE65) to access the 11-cis retinal dehydechromophore. Research efforts dedicated on the progression of a gene-based therapy for the treatment of LCA2. Such gene therapy approaches were extremely successful in canine, porcine and rodent LCA2 models. The recombinant AAV2.hRPE65v2 adeno-associated vector contained the RPE65 cDNA and was replication deficient. Itsin vitroinjection in target cells induced RPE65 protein production. The gene therapy trials that were so far conducted for inherited retinopathies have generated promising results. Phase I clinical trials to cure LCA and choroideremia demonstrated that adeno-associated viral vectors containing RPE genes and photoreceptors respectively, could be successfully administered to inherited retinopathy patients. A phase III trial is presently ongoing and if successful, it will lead the way to additional gene therapy attempts to cure monogenic, inherited retinopathies.
authors.affiliation: Department of Ophthalmology Birmingham & Midland Eye Centre, City Hospital NHS Trust, Birmingham B18 7QH, UK.
authors.forename: Walid
authors.initials: W
authors.lastname: Sharif
authors.affiliation: Institute of Ophthalmology, University College London 11-43 Bath St, London EC1V 9EL, UK.
authors.forename: Zuhair
authors.initials: Z
authors.lastname: Sharif
keywords: Leber's congenital amaurosis; Leber's congenital amaurosis type 2; achromatopsia; choroideremia; cyclic nucleotide gated channel alpha 3; gene therapy; retina; retinoid isomerohydrolase