Mefunidone Inhibits Inflammation, Oxidative Stress, and Epithelial-Mesenchymal Transition in Lens Epithelial Cells

Inflammation, oxidative stress, and epithelial-mesenchymal transition (EMT) play crucial roles in forming posterior capsular opacification (PCO), particularly in fibrotic PCO. Here we investigated the protective effects of mefunidone (MFD), a novel compound with potent antifibrotic properties, which could be useful in preventing PCO.

We utilized an extracapsular lens extraction (ECLE) surgery in mice to simulate the development of PCO in vivo. Treatment was performed immediately postsurgery through the intracameral injection of MFD solution. Expression levels of EMT and inflammatory markers were analyzed using Western blot, qRT-PCR, immunofluorescence, and hematoxylin and eosin staining. Additionally, the oxidative stress indicator malondialdehyde and glutathione expression were monitored to assess the oxidative stress response. In vitro experiments, TGF-β2, and H2O2 were used to treat lens epithelial cells to induce EMT and oxidative stress models, respectively. These models were employed to explore the effects of MFD and investigate its underlying mechanisms.

Compared to the model group, the group treated with anterior chamber MFD injection effectively suppressed inflammation, oxidative stress, and fibrotic responses within the capsular bag after ECLE and partially inhibited the downregulation of the epithelial marker E-cadherin. To further elucidate the underlying mechanisms, we discovered that MFD treatment in vitro remarkably reduced inflammation, decreased the production of reactive oxygen species, and suppressed the phosphorylation of TGF-β/SMAD as well as MAPK/ERK, thereby inhibiting the occurrence of EMT.

Our findings substantiate the efficacy of MFD in treating PCO and provide insights into its potential mechanisms of action.