Characterization of adeno-associated viral transduction of retinal ganglion cells in adult and old mice.

Adeno-associated viral (AAV) vectors are being used increasingly in developing treatments for age-related ocular diseases, including those impacting retinal ganglion cells (RGCs), the output neurons of the eye. However, the effects of persistent transgene expression on RGC structure and function have not been thoroughly investigated. In this study, viral transduction was studied in parallel cohorts of adult (3-6 month-old) and old (18-24 month-old) mice and the persistence of viral expression characterized in aging mice. Age-related differences in viral transduction were investigated using in vivo imaging and immunohistochemical analyses. Effects of viral transduction on RGC function were examined using calcium imaging in intact-isolated retinal preparations. We demonstrate that AAV expression persists over 18 months following a single viral injection. Decreases in RGC density observed in AAV-injected aged mice were not significantly different from age-matched controls, suggesting age-related RGC loss unrelated to viral injection. Moreover, mice aged to 18 months post-AAV injection and old mice had similar loss of RGC function when compared to adult mice, despite differences in transduction durations. Our study found no deleterious effects of AAV transduction and highlights the potential of AAV-based methods for long-term RGC labeling and therapeutic strategies.