Microglia-independent rAAV-induced inflammation causes persistent ocular immune dysregulation rescued by S1P receptor modulation - PubMed
5 hours ago
- #gene therapy
- #inflammation
- #T cells
- rAAV vectors cause inflammation in the eye, posing challenges for gene therapy efficacy and safety.
- Preclinical models show persistent subclinical inflammation even after acute inflammation resolves.
- Study in Cx3cr1CreER:R26-tdTomato+/- mice reveals sustained microglial dysregulation and CD3+ T cell retention up to 50 days post-injection.
- Microglia-independent mechanisms initiate gene therapy-associated uveitis (GTAU), but T cells are essential for inflammation and microglial activation.
- Sphingosine-1-phosphate receptor modulation effectively prevents acute and long-term inflammation by inhibiting T cell recruitment.
- Findings challenge the idea of microglia-driven ocular inflammation and highlight T cell immunomodulation as a key strategy for maintaining ocular homeostasis.