Integrating epidemiology and mechanistic studies links PFAS exposure to ocular diseases and implicates PFOS-associated glaucoma risk through the PI3K/Akt-MMP3 axis.

Authors

Mengxin Tian, Wenxia Bu, Xinhang Cheng, Zengxu Shen, Yue Fei, Luyao Jiang, Mingjing Sun, Zihan Wang, Jing Xiao, Demin Cheng, Xinyuan Zhao

Published in

Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. Pages 116416. Sep 30, 2026. Epub Sep 30, 2026.

Abstract

Perfluoroalkyl substances (PFAS) pose health risks, but their association with glaucoma, cataracts, and age-related macular degeneration remains uncertain. First, a cross-sectional analysis of NHANES (2005-2008) was performed using multiple logistic regression and mixture models, including weighted quantile sum (WQS), quantile g-computation (QGC), and Bayesian kernel machine regression (BKMR), to examine single and mixed PFAS exposures in relation to ocular diseases. Second, Mendelian randomization was applied to further explore the PFOS-glaucoma association. Third, network toxicology and in vitro experiments were employed to generate mechanistic hypotheses. Cross-sectional results suggested positive associations between PFOS and glaucoma, and between PFNA and cataracts. Sex-stratified analyses revealed positive associations of PFOS with glaucoma in females, and in males, of PFDA with glaucoma and PFNA with cataracts. Mixture models suggested that PFOS may be a driving factor for glaucoma risk. Sensitivity analyses yielded results generally consistent with the primary findings. Mendelian randomization supported a positive PFOS-glaucoma association. Network toxicology and in vitro experiments indicated that PFOS activates PI3K/Akt signaling and reduces MMP3 expression. LY294002 treatment partly restored MMP3 expression, supporting a role for PI3K/Akt signaling in this response. These results suggest that the PI3K/Akt-MMP3 axis may be involved in PFOS-induced extracellular matrix changes in trabecular meshwork cells.

PMID:
42815678
Bibliographic data and abstract were imported from PubMed on 01 Oct 2026.

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