In vitro cell subtype-specific transduction of adeno-associated virus in mouse and marmoset retinal explant culture.

Adeno-associated virus (AAV) is a non-pathogenic human parvovirus that can infect both non-proliferating and proliferating cells. Owing to its favorable safety profile, AAV is regarded as suitable for clinical purposes such as gene therapy. The target cell types of AAV depend largely on the serotype. In the retina, AAV has been used to introduce exogenous genes into photoreceptors, and photoreceptor-specific enhancers/promoters are used in most cases. Therefore, serotype specificity of AAV in retinal subtypes is unclear, particularly in vitro. We compared its infection profile in mouse and monkey retinas using EGFP under the control of the CAG promoter, which expressed the gene ubiquitously and strongly regardless of cell type. AAV1, 8, and 9 infected the horizontal cells when an embryonic day-17 retina was used as a host. Amacrine cell was also a major target of AAVs, and a small number of rod photoreceptors were infected. When adult retinas were used as a host, the main target of AAV was Müller glia. A small number of rod photoreceptors were also infected. In the adult common marmoset retina, rod and cone photoreceptors were efficiently infected by AAV1, 8, and 9. A portion of the Müller glia and amacrine cells were also infected. In summary, the infection specificity of different AAV serotypes did not differ, but was dependent on the stage of the host retina. In addition, infection specificities differed between mature marmoset retinas and mature mouse retinas.