Characterization of the ocular inflammatory response to AAV reveals divergence by sex and age.

ABSTRACT: Progress for ocular adeno-associated virus (AAV) gene therapy has been hindered by AAV-induced inflammation, limiting dose escalation and long-term efficacy. Broadly, the extent of inflammatory responses alters with age and sex, yet these factors are poorly represented in pre-clinical development of ocular AAV gene therapies. Here, we combined clinical imaging, flow cytometry, and bulk sequencing of sorted microglia to interrogate the longitudinal inflammatory response following intravitreal delivery of AAV2 in young (3-month-old), middle aged (9-month-old), and old (18-month-old) Cx3cr1-creER:R26tdTomato^+/- mice of both sexes. Young males and females exhibited a similar dynamic response, with peak inflammation evident at days 10-12 and signs of clinical resolution by day 28. Ho

SUBMITTER: Clare AJ 

PROVIDER: S-EPMC11897812 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature