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AJ Lotery, TA Derksen, SR Russell, RF Mullins, GS Yang, KK Kopp, CG Eastman, EM Stone, BL Davidson; Trophism of AAV2 and AAV5 Vectors in the Non-human Primate Retina . Invest. Ophthalmol. Vis. Sci. 2002;43(13):4609.
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Purpose: To evaluate gene transfer with adeno-associated (AAV) viral vectors, serotypes 2 and 5 in the non-human primate retina Methods: Three rhesus monkeys underwent pars plana vitrectomy. A modified Hamilton syringe with a 41 gauge soft tipped cannula was passed through the vitreous cavity and multiple sub-retinal injections of a vector solution were placed in the sub-retinal space. The vector solution consisted of an equal mixture of CMVAAV2DSRed and CMVAAV5EGFP. Following surgery the animals were examined by ophthalmoscopy and electrophysiology before being sacrificed at 5, 8 or 9 months after surgery. The retinas were evaluated at the final endpoint by routine histology and immunohistochemistry. Results: One animal exhibited self-limited choroidal effusions post-operatively. There were no other surgical complications. All three animals exhibited normal electrophysiology following surgery. In vivo green fluorescence was visible one month following surgery in the two animals that did not develop choroidal effusions. One of these two animals was sacrificed 5 months after surgery and exhibited robust green fluorescence microscopically. This fluorescence was confirmed as originating from rod photoreceptors by immunohistochemistry. When the second animal was sacrificed at 9 months, green fluorescence was also detected but at a lower level. Conclusion: AAV5 appears to exhibit greater trophism for rod photoreceptors than AAV2 in the non-human primate retina. Transduction was most effective in the absence of post-operative effusion. With the conditions employed in this experiment, expression of the transgene appears to decrease with time.
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