ArticleFrontiers in immunology2026
Intravitreal AAV vector delivery induces integrin-dependent ocular inflammation, complement activation, and antiviral and DNA damage responses.
Article in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Intravitreal delivery of adeno-associated virus (AAV) vectors offers a promising, minimally invasive strategy for retinal gene therapy, but remains limited by dose-dependent intraocular inflammation. Corticosteroid therapy, the current standard for managing gene therapy-associated uveitis (GTAU), can be ineffective or contraindicated, highlighting the need for alternative immunomodulatory approaches and deeper understanding of AAV-induced inflammation. Methods: Using porcine and mice models, we characterized immune responses triggered by AAV2.7m8 vector. Results: Consistent with previous data for this serotype, AAV-mediated transgene expression localized predominantly to retinal ganglion cells, although photoreceptor, bipolar, amacrine, horizontal, and glia cells were also transduced. Despite prophylactic methylprednisolone, AAV-treated animals developed GTAU, accompanied by increased MCP-1, IP-10, MIP-1α and IL-6 levels in ocular humors, along with microglial activation and peripheral leukocyte infiltration. Transcriptomic analysis revealed upregulation of antiviral interferon responses across all retinal cell populations, together with complement and DNA damage pathways. Accordingly, functional assays confirmed complement C3a accumulation in ocular humors and presence of γH2AX Conclusion: Our work identified new markers of ocular inflammation and potential targets to modulate GTAU.
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