Activation of the cGAS-STING pathway depends on the recognition of intracellular nucleic acids,23 including cytoplasmic mtDNA or oxidized mtDNA.42,69 A previous study reported that HS mediated mtDNA oxidation in an in vitro dry eye model.40 However, oxidized mtDNA was not the main agent responsible for cGAS-STING pathway activation in dry eye in this study, since inhibiting mtDNA oxidation by exogenous 8-OHDG did not downregulate the cGAS-STING pathway (Fig. 4i, j). This evidence concerns the gene STING1 and Keratoconjunctivitis sicca.