Gene therapy for retinal and choroidal diseases

The eye is a small compartment separated from the systemic circulation by the blood-ocular barriers, providing advantages for intraocular gene transfer - an approach which is being investigated for several types of retinal and choroidal diseases. A compelling application is gene replacement for homozygous loss-of-function mutations in genes differentially expressed in photoreceptors or retinal pigmented epithelial (RPE) cells that result in retinal degeneration. Considerable progress has been made in this area, including demonstration of return of visual function in RPE65^-/- dogs after subretinal injection of adeno-associated viral vectors encoding RPE65, providing groundwork for a clinical trial in patients with Leber's Congenital Amaurosis. Proof of principle has been provided for intraocular gene transfer of ribozymes for dominantly inherited retinal degenerations. Survival factor gene therapy shows promise for treatments that may be used in multiple retinal degenerations. Transduction of intraocular and/or periocular cells with constructs that encode antiangiogenic proteins provides a new approach for sustained local delivery treatment of retinal and choroidal neovascularisation. While considerable investigation remains to work out critical details, there is substantial evidence suggesting that in the near future, gene therapy-based treatments will be an important addition to what is currently offered to patients with retinal and/or choroidal diseases.