AAV9-delivery of interleukin-37b gene prevents recurrent herpetic stromal keratitis via the SIGIRR pathway in mice.

Ocular herpes simplex virus type I (HSV-1) infection can lead to herpes stromal keratitis (HSK), a condition that may recur throughout a person's life and often results in progressive corneal scarring, which ultimately causes visual impairment. Since existing antiviral agents are ineffective against recurrent HSK, we aimed to explore a strategy to prevent or control recurrent HSK. Adeno-associated virus (AAV) delivery system can transduce target genes into corneal epithelial cells and establish long-term stable gene expression, and providing a promising approach for the prevention and management of recurrent HSK. In this study, interleukin-37 (IL-37), an anti-inflammatory factor, is identified as a therapeutic agent for recurrent HSK via the SIGIRR pathway. AAV9-IL-37bΔ1-45 gene therapy prevents recurrent HSK in HSV-1 latently infected mice and alleviates corneal injury in mice with HSK. In conclusion, our present study establishes a strong foundation for the prevention of recurrent HSK through AAV9-IL-37bΔ1-45 gene therapy.