544. Comparison of AAV Serotype2 Transduction by Various Delivery Routes to the Mouse Eye

AAV gene therapy has demonstrated success for the treatment of several ocular diseases with the tropism and efficiency of AAV retinal transduction being a function of the route of administration. Subretinal injection has been the primary route to deliver AAV to the retina but this injection route carries surgical complications and transduction remains localized to the area of retinal detachment. Despite the use of suprachoroidal injections for ocular drug delivery in large animal models, this route has not been comprehensively compared to AAV vector transduction following other administration routes in mice. AAV serotype 2 (AAV2) was used to deliver a self-complementary CMV-GFP reporter cassette via intrastromal, intracameral, intravitreal, subretinal, or suprachoroidal injections. These injections were validated by fundoscopy and optical coherence tomography at the time of injection. Transduction was assessed six weeks later by fundoscopy and whole globes were evaluated for histology. Transduction of the stroma, ciliary body, retinal ganglion cells, outer retina, and retinal pigment epithelium could be seen in the various routes of delivery to the eye. In particular, the transduction of multiple retinal layers throughout the retina without the damage of retinal detachment and widespread distribution makes suprachoroidal injections a better delivery route than to subretinal injection.