Polystyrene and polyvinyl chloride microplastics exposure induces ocular surface inflammation by causing mitochondrial damage and lipid metabolic disruption

Microplastics (MPs), particularly polystyrene (PS) and polyvinyl chloride (PVC), are pervasive environmental pollutants implicated in ocular surface damage through poorly understood molecular mechanisms. Here, we elucidate the pathways underlying PS/PVC-induced ocular surface inflammation. In vitro, PS and PVC particles were internalized by human corneal epithelial cells - transformed (HCE-T) cells, inducing cytotoxicity and robust pro-inflammatory responses. In vivo, PS/PVC exposure elicited dry eye-like phenotypes in the murine ocular surface. Integrated transcriptomic and metabolomic analyses revealed that PS/PVC trigger inflammatory cascades via mitochondrial damage and disruption of lipid metabolism. Specifically, aberrant opening of the mitochondrial permeability transition pore (mPTP), leakage of mitochondrial DNA (mtDNA), and dysregulation of lipid metabolism-associated genes LIPG and GRB14 emerged as key drivers of inflammation in HCE-T cells. Concurrently, PS/PVC-induced energy stress enhanced lipid droplet-mitochondria tethering. Notably, corneal inflammation was markedly attenuated by treatment with the mitochondria-targeted antioxidant SkQ1 and an adiponectin receptor agonist. Collectively, these findings delineate a mitochondria- and lipid metabolism-mediated mechanism for PS/PVC-induced ocular surface inflammation, offering mechanistic insights and potential therapeutic strategies for mitigating microplastic-associated ocular toxicity.