Study on the Role of FGF9/ERK/MMP9 Pathway in Age-Related Cataract and in (-)-Epigallocatechin-3-gallate Protecting Lens Epithelial Cells From Apoptosis.

Age-related cataract (ARC) is the most prevalent form of cataract. Oxidative stress-induced apoptosis of lens epithelial cells (LECs) is a major pathogenic factor, but its underlying molecular mechanisms remain incompletely understood. This study investigated the roles of FGF9, ERK, and MMP9 in ARC and examined whether the FGF9/ERK/MMP9 pathway is involved in the protective effects of (-)-epigallocatechin-3-gallate (EGCG) against LEC apoptosis. FGF9 and MMP9 were downregulated at both the mRNA and protein levels in ARC mice and H2O2 (200 µM)-treated HLE-B3 cells as determined by immunohistochemistry, Western blotting and qRT-PCR. FGF9 overexpression increased cell viability and reduced apoptosis in H2O2-treated HLE-B3 cells, as demonstrated by CCK-8 and Hoechst 33342 staining. EGCG treatment improved cell viability and increased FGF9 expression in H2O2-treated cells and lens tissues from ARC mice. Conversely, FGF9 knockdown attenuated the protective effect of EGCG. Further experiments suggested that FGF9 may contribute to the anti-apoptotic effects of EGCG by modulating ERK phosphorylation and MMP9 expression. ERK activation by TBHQ increased the viability of H2O2-treated HLE-B3 cells, whereas ERK inhibition with PD98059 attenuated the protective effects of EGCG and decreased MMP9 expression. Moreover, MMP9 knockdown increased cleaved caspase-9 expression and was accompanied by increased apoptosis in LECs. These findings suggest that the FGF9/ERK/MMP9 pathway is involved in oxidative stress-induced LEC apoptosis and may contribute, at least in part, to the protective effects of EGCG in experimental models of ARC.