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Progress in gene therapy for retinal degenerationM. B. Reichel
Introduction: The research for molecular mechanisms of inherited retinal disease has significantly progressed with cloning of many genes for retinal degeneration. The development of vector technology hat the same time has opened the door for a new therapeutical strategy: Gene transfer and gene therapy. The most important steps in the development of gene therapy for retinal degeneration and the latest results are explained.
Methods: Several vector systems have been evaluated for efficient gene transfer into the retina (e.g. AV, AAV, and HIV). The best results so far have been achieved with adeno associated virus (AAV). Gene transfer can only be sufficiently analysed in vivo. The retinal degeneration slow (rds) mouse is a well-characterised animal model, which lacks a functional gene encoding peripherin/rds, a protein with a role in photoreceptor outer, segment structure. Homozygous null rds mutants do not produce outer segments. This model was used to test a gene replacement strategy.
Results: Subretinal injection of recombinant AAV containing peripherin/rds cDNA driven by a photoreceptor specific promoter expressed the transgene and could correct the rds defect morphologically and functionally.
Discussion: The feasibility of gene replacement therapy for retinal degeneration was demonstrated. The open questions of ocular gene therapy, other strategies based on gene transfer and problems of gene regulation will be discussed.
Klinik und Poliklinik für Augenheilkunde, Universität Leipzig, Liebigstrasse 10, 04103 Leipzig