Discussion
In this study, we uncover the interplay between autophagy and the TGF-β2/Smad pathway in the pathogenesis of POAG. We observed increased autophagic activity in TM tissues from POAG patients and in TM tissues of aging healthy individuals. In human primary TM cells, we confirmed that autophagy becomes activated in the context of cellular senescence and the development of POAG, which further facilitates fibrotic progression via the TGF-β2/Smad signaling pathway. These findings underscore the important role of autophagy in POAG pathogenesis and confirm senescence as a pivotal risk factor.
Methods
To assess autophagy activity and its relationship with fibrosis, we analyzed TM tissues from POAG patients and healthy donors. Autophagic activity in human TM tissues was measured through immunohistochemical analyses. An in vitro aging model using chronic H2O2 treatment was established to investigate the change of fibrosis in TM cells. Additionally, we used dexamethasone-treated TM cells as a POAG model to explore the role of autophagy in fibrotic progression. The involvement of the TGF-β2/Smad signaling pathway was investigated through western blot analysis and quantitative real-time PCR.
Results
This study reveals increased autophagic activity in tissues from POAG patients and an age-related upregulation of autophagy in healthy human TM tissues. In the H2O2-induced aging model, TM cells displayed both elevated autophagic activity and fibrosis. Further investigation showed that enhanced autophagy activity promoted fibrotic progression via activation of the TGF-β2/Smad signaling pathway. Similarly, in the dexamethasone-treated TM cell model, autophagy was found to exacerbate fibrosis, aligning with observations in the aging model.