OBJECTIVES:Fibrosis is a complex process involved in multiple diseases that result in organ injury and failure. Cataract, one common form of ocular fibrosis, is a main cause of blindness worldwide, and surgery may be the only cure. In this regard, epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs) is the primary cause of anterior subcapsular cataract (ASC). This study aimed to investigate the mechanism by which 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNPase) regulates the function of EMT in LECs. MATERIALS AND METHODS:A mouse model of ASC was used to observe the expression of CNPase in the lens and correlate its expression changes with lens EMT. Furthermore, the effects of CNPase on cell migration and cell proliferation were evaluated by transwell migration, wound healing and EdU staining assays. Finally, Western blotting and immunofluorescence were used to assess the mechanical properties potentially involved in the regulation of EMT by CNPase. RESULTS:The expression of CNPase was upregulated in LECs during the EMT process in mice with ASC. Notably, CNPase significantly promoted the proliferation, migration and EMT of LECs in vitro. Interestingly, the EMT-promoting mechanism of CNPase may be achieved by targeting the Notch signalling pathway. CONCLUSIONS:Considering the involvement of EMT in ASC, both CNPase and the Notch signalling pathway may be therapeutic targets for the treatment of cataracts.
KEYWORDS: 2',3'-cyclic-nucleotide 3'-phosphodiesterase, anterior subcapsular cataracts, epithelial-mesenchymal transition, fibrosis, lens epithelial cell, notch signalling pathway