Cataract is the leading cause of visual impairment,and posterior capsular opacification(PCO)is the most common long-term complication of modern cataract surgery,which can cause severe visual impairment after surgery.T...Cataract is the leading cause of visual impairment,and posterior capsular opacification(PCO)is the most common long-term complication of modern cataract surgery,which can cause severe visual impairment after surgery.The proliferation,migration,and epithelial-mesenchymal transition(EMT)of residual lens epithelial cells(LECs)stimulated by growth factors and cytokines,are the key pathological mechanisms involved in the development of PCO.This study demonstrated that non-steroidal anti-inflammatory drug(NSAID),bromfenac,was capable of effectively inhibiting cell migration,overexpression of EMT markers,such as fibronectin(FN),matrix metalloproteinase 2(MMP2),α-smooth muscle actin(α-SMA),and transcription factor Snail,and extracellular signal-regulated kinase(ERK)/glycogen synthase kinase-3β(GSK-3β)signaling induced by transforming growth factor-β2(TGF-β2)in vitro.The inhibitory effect of bromfenac on TGF-β2-induced EMT was also verified on a primary lens epithelial cell model using human anterior capsules.Furthermore,based on ultrasonic spray technology,we developed a drug-eluting intraocular lens(IOL)using poly(lactic-co-glycolic acid)(PLGA)with sustained bromfenac release ability for the prevention of PCO development.In the rabbit models of cataract surgery,bromfenac-eluting IOL exhibited remarkable PCO prevention and inflammation suppression effects with excellent biocompatibility.In conclusion,bromfenac can inhibit TGF-β2-induced cell migration and the EMT of LECs via ERK/GSK-3β/Snail signaling.The present study offers a novel approach for preventing PCO through PLGA-based drug sustained-release IOLs.展开更多
基金This study was supported by the National Natural Science Foundation of China(Grant Nos.82070939,22005265,81870641,and 81800809)the National Key R&D Program of China(No.2018YFC1106104)+1 种基金Key Research and Development Project of Zhejiang Province of China(No.2020C03035)and the Joint Funds of the Zhejiang Provincial Natural Science Foundation of China(Grant No.LBY21E030002).
文摘Cataract is the leading cause of visual impairment,and posterior capsular opacification(PCO)is the most common long-term complication of modern cataract surgery,which can cause severe visual impairment after surgery.The proliferation,migration,and epithelial-mesenchymal transition(EMT)of residual lens epithelial cells(LECs)stimulated by growth factors and cytokines,are the key pathological mechanisms involved in the development of PCO.This study demonstrated that non-steroidal anti-inflammatory drug(NSAID),bromfenac,was capable of effectively inhibiting cell migration,overexpression of EMT markers,such as fibronectin(FN),matrix metalloproteinase 2(MMP2),α-smooth muscle actin(α-SMA),and transcription factor Snail,and extracellular signal-regulated kinase(ERK)/glycogen synthase kinase-3β(GSK-3β)signaling induced by transforming growth factor-β2(TGF-β2)in vitro.The inhibitory effect of bromfenac on TGF-β2-induced EMT was also verified on a primary lens epithelial cell model using human anterior capsules.Furthermore,based on ultrasonic spray technology,we developed a drug-eluting intraocular lens(IOL)using poly(lactic-co-glycolic acid)(PLGA)with sustained bromfenac release ability for the prevention of PCO development.In the rabbit models of cataract surgery,bromfenac-eluting IOL exhibited remarkable PCO prevention and inflammation suppression effects with excellent biocompatibility.In conclusion,bromfenac can inhibit TGF-β2-induced cell migration and the EMT of LECs via ERK/GSK-3β/Snail signaling.The present study offers a novel approach for preventing PCO through PLGA-based drug sustained-release IOLs.
