The vertebrate retina is a light-sensitive, stratified layer of neuronal cells that lines the interior of the eye. Photons of light absorbed by photosensitive retinal neurons are converted into an electrochemical signal ultimately passed to the brain to process visual images. Retinal ganglion cells (RGCs), the terminal neurons within the retina, pass these signals to the brain via axons bundled in the optic nerve. RGCs in the retina as well as their axons in the optic nerve are highly sensitive to damage observed in glaucoma and other optic neuropathies. Due to their position in the inner most portion of the retina, RGCs are accessible to molecular treatments via intravitreal injections. Our experiments explore the short and long-term survival of RGCs following intravitreal injection of AAV2-Cre recombinase or a control virus in wild type mice. Retinal flat mounts and axonal cross sections were assayed for viral transduction and RGC survival at various time points post injection. Short-term experiments demonstrate that AAV2-mediated Cre recombinase expression is efficient and well tolerated in the wt mouse retina. However, Cre toxicity of RGC was observed at 5 weeks post injection of AAV2-Cre. Collectively these findings suggest that viral delivery of Cre recombinase may be an effective strategy for short-term experimental studies, but not as useful for studies requiring persistent Cre expression.