Chlorinated Polyfluoroalkyl Ether Sulfonic Acids (Cl-PFESAs) Are Associated with Eye Diseases in Humans and Eye Toxicity in Zebrafish

Evidence from animal experiments has shown that chlorinated polyfluoroalkyl ether sulfonic acids (Cl-PFESAs) can induce vision dysfunction in zebrafish. However, environmental epidemiological evidence supporting this hypothesis remains limited. In our case-control study, samples collected from 270 individuals (135 controls and 135 cases) from the Isomers of C8 Health Project data were analyzed for Cl-PFESAs. We also repeated our analysis on zebrafish to support our findings in humans and to decipher the mechanism underlying Cl-PFESA eye toxicity. The serum levels of per- and polyfluoroalkyl substances (PFASs) and alternatives were significantly higher in the cases than in the controls. Higher serum Cl-PFESA levels were associated with greater odds of eye diseases, and the trend showed a statistically significant dose-dependent relationship. The Shapley additive explanations (SHAP) value indicated that 8:2 Cl-PFESA was the dominant eye disease risk factor among the 13 studied PFASs. In zebrafish experiments, Cl-PFESAs induced eye toxicity in adult zebrafish by oxidative damage and cell apoptosis. Compared to the control group, there was significantly reduced thicknesses of the inner plexiform layer (IPL), outer plexiform layer (OPL), and retinal tissue in the zebrafish exposed to Cl-PFESAs. Our study provides human clinical and animal experimental data, showing that exposure to PFASs increases the odds of the development of eye toxicity.