Gene therapy for ocular neovascularization.

Ocular neovascularization is a major cause of blindness and visual disability in developed countries. There has been considerable recent progress identifying molecular signals that participate in ocular neovascularization and it appears that imbalances between stimulatory and inhibitory proteins contribute. Re-establishing balance by ocular gene transfer to block stimulators or increase expression of endogenous inhibitors is an appealing therapeutic approach, because it provides a potential means to achieve sustained intraocular effects with little impact on the rest of the body. Proof-of-concept has been provided in animal models using several vector systems and several transgenes and completion of a phase I study testing intraocular injection of an adenoviral vector expressing pigment epithelium-derived factor is an important milestone that will help to accelerate future progress. It is likely that additional vectors and transgenes will enter clinical trials in the near future. This report discusses the rationale and experimental evidence regarding several candidate transgenes.