Assessing the therapeutic effects of DPP4 Inhibitors on TGF-β2-induced Lens Opacity

Posterior capsular opacification (PCO) is a common complication following cataract surgery, resulting from the epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs). PCO continues to represent a significant public health challenge due to its detrimental impact on visual outcomes, with many patients requiring additional interventions. In this study, we evaluated the potential efficacy of DPP4 inhibitors—specifically Sitagliptin, Saxagliptin, and Vildagliptin—in mitigating TGF-β-induced EMT in LECs. We hypothesized that these inhibitors could reduce fibrotic changes in LECs and slow the progression of PCO. Human LECs and mouse lenses were pretreated with DPP4 inhibitors prior to exposure to TGF-β2. The expression of EMT markers, including fibronectin, vimentin, and α-smooth muscle actin, was assessed using immunostaining, Western blotting, and RT-qPCR. Both cellular and lens explant cultures demonstrated that DPP4 inhibitors attenuated the expression of TGF-β2-induced EMT markers by blocking Smad2 phosphorylation. Notably, lens explant cultures treated with Vildagliptin showed a reduction in lens opacity induced by TGF-β2. These findings suggest that DPP4 inhibitors, particularly Vildagliptin, may offer a novel, non-invasive pharmacological approach to preventing PCO by targeting TGF-β signaling pathways. • DPP4 inhibitors are potential therapeutic candidates for preventing lens opacity. • DPP4 inhibitors suppress EMT by inhibiting the TGF-β2/Smad2 signaling pathway. • Vildagliptin significantly reduces TGF-β2-induced lens opacity in ex-vivo models. • DPP4 inhibitors may provide additional benefits for diabetic patients with PCO.