Resaerch

A key aspect of our research is investigating how endogenous cytoplasmic Alu cDNA induces RPE degeneration through reverse transcription. Alu cDNA is generated via cytoplasmic LINE-1 ORF2p-mediated reverse transcription of Alu RNA, with self-priming facilitating the process. Once formed, Alu cDNA activates cGAS, triggering the release of mitochondrial DNA (mtDNA), which further amplifies cGAS activation. This activation leads to the production of cGAS-driven type I interferons (IFNs), which, in turn, stimulate caspase-4/11 activation and NLRP3 inflammasome-mediated IL-18 secretion. The autocrine and paracrine signaling of IL-18 ultimately drives RPE cell death through Myd88. Understanding this mechanism will provide a foundation for the rational design of therapeutics to treat advanced AMD.