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Prevention of Secondary Cataracts by Targeting Proliferating Lens Epithelial Cells by Somatic Gene Therapy


, : Prevention of Secondary Cataracts by Targeting Proliferating Lens Epithelial Cells by Somatic Gene Therapy. ARVO Annual Meeting Abstract Search & Program Planner : Abstract No 2354

Purpose: Posterior capsule opacification (PCO) is a common complication that affects 30-50% of patients within two years after cataract surgery. The proliferation of residual lens epithelial cells (LECs) after surgery is responsible for PCO. It most frequently occurs following surgery in children with congenital cataracts. Actually PCO may be treated with YAG-capsulotomy. However this treatment is expensive and presents some contre-indications in terms of costs, ocular complications, feasibility and efficacy. The authors describe preliminary results of a patented procedure based on somatic gene therapy, which is intended to prevent cell growth on the posterior capsule. Methods: Lens capsules were isolated from pig eyes, sterile PMMA capsular tension rings inserted and the preparations placed in culture medium. Pig lens capsules were then infected by a non-replicative recombinant adenovirus expressing the thymidine kinase from HSV1 (Ad-HSV1TK) or the green fluorescent protein (GFP) in a cell-specific manner. LEC-specific expression of the foreign genes delivered by the recombinant adenoviruses is achieved with one of three promoters: a Major Intrinsic Protein gene promoter (Ad-MIP-HSV1TK), a betaA3/A1-crystallin gene promoter (Ad-betaA3/A1-cry-HSV1TK), a alphaB-crystallin promoter (Ad-alphaB-cry-HSV1TK). LECs infected by Ad-HSV1TK undergo cell death in the presence of the prodrug ganciclovir (GCV). Lens capsules are cultured for 4 weeks and examined every 5 days for LECs proliferation state. Results: Sixty pig lens capsules were isolated. Twenty were used to assess the conditions of organo-culture and infections by the recombinant adenoviruses. We only observed GFP expression in LECs infected by adenoviruses expressing GFP under the control of alphaB-crystallin, betaA3/A1-crystallin or Major Intrinsic Protein promoter. No PCO of lens capsule cultures by LECs were observed for a viral dose of 7.105and 5.106pfu Ad-alphaBcry-HSV1TK in the presence of GCV compared to the lens capsules controls covered by LECs in 10 days. Conclusion: Although further studies will be necessary, the delivery of a suicide gene specifically expressed in LECs by recombinant adenovirus may be considered as a preventive measure for PCO when used at time of primary cataract surgery.

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