RETROVIRUS-MEDIATED GENE-TRANSFER TARGETED TO RETINAL PHOTOCOAGULATION SITES

Diabetic retinopathy is a major cause of acquired blindness due to the development of retinal neovascularization and associated traction ret inal detachment. It is commonly treated with retinal photocoagulation therapy; however, progression to blindness remains a significant probl em. To determine the feasibility of adjunctive anti-angiogenic gene th erapy, we evaluated the capability of retroviral vectors, which transf er exogenous genes only into dividing cells, to transfer and express a beta-galactosidase gene selectively into photocoagulation sites. Thir ty-five rabbits received 30 retinal photocoagulation burns in the righ t eye followed 2 days later by beta-galactosidase (G1nBgSvNa) or contr ol (G1XSvNa) vector injection into the subretinal space. P-galactosida se expression was observed in the photocoagulation sites from 5 days a fter vector administration (31.7 +/- 7.0 %) to 12 weeks (6.7 +/- 3.4 % ). Immunohistochemical studies of the treated retinas using antibody B er-MAC3 and anti-cytokeratin antibodies revealed that transduced cells were macrophages and retinal pigment epithelial cells. To determine f easibility in a primate, two monkeys received 10 laser burns in the ma cula superior to the fovea followed 2 days later by G1nBgSvNa vector. beta-galactosidase expression was found in photocoagulation sites and foveal retina was well preserved. We conclude that gene transfer to re tinal photocoagulation sites provides stable expression of the transdu ced gene with relatively high efficiency. This feasibility study sugge sts the possibility of transferring genes encoding for anti-angiogenic factors into photocoagulation sites to improve the efficacy of laser photocoagulation therapy.