Assessing the therapeutic effects of DPP4 Inhibitors on Lens Opacity

Posterior capsular opacification (PCO) is a complication that frequently arises following cataract surgery and results from epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs). Currently, PCO remains a quite serious public health burden, as it affects visual outcomes, and a high percentage of affected patients need further interventions. In this study, we investigated the inhibition of TGF-β-induced EMT of LECs by DPP4 inhibitors (DPP4i), more specifically, Sitagliptin, Saxagliptin, and Vildagliptin, as we hypothesized them to reduce the fibrotic changes in LECs and inhibit the development of PCO. We pretreated human LECs and mouse lenses with DPP4i and then exposed them to TGF-β2. We measured the expression of the EMT markers, including fibronectin, vimentin, and α-smooth muscle actin, through immunostaining, Western blot analysis, and RT-qPCR analyses. Cellular and lens cultures showed that DPP4i attenuated the expression of TGF-β2-induced EMT markers. The lens explant culture image further showed that Vildagliptin treatment alleviated lens opacity induced by TGF-β2 exposure. Our results confirm the working hypothesis that DPP4 inhibitors demonstrate anti-EMT effects. This study provides a new outlook on non-invasive pharmacological strategy for the prevention of PCO by targeting the TGF-β signaling. Further investigation is needed to confirm these findings in animal models and evaluate the long-term impact of DPP4 inhibitors on lens capsule clarity and post-cataract surgery visual outcomes.