Prophylaxis of posterior capsule opacification through autophagy activation with indomethacin-eluting intraocular lens  

作　　者：Xiaobo Zhang Jing Wang Jingwei Xu Wen Xu Yin Zhang Chenqi Luo Shuang Ni Haijie Han Xingchao Shentu Juan Ye Jian Ji Ke Yao 

机构地区：[1]Eye Center,The Second Affiliated Hospital,School of Medicine,Zhejiang University,Hangzhou,310009,PR China [2]Zhejiang Provincial Key Lab of Ophthalmology,The Second Affiliated Hospital,School of Medicine,Zhejiang University,Hangzhou,310009,PR China [3]MOE Key Laboratory of Macromolecule Synthesis and Functionalization of Ministry of Education,Department of Polymer Science and Engineering,Zhejiang University,Hangzhou,310027,PR China

出　　处：《Bioactive Materials》2023年第5期539-550,共12页生物活性材料（英文）

基　　金：This work was supported by the National Key Research and Development Program of China(Grant numbers 2020YFE0204400);National Natural Science Foundation of China(Grant numbers 82271063,82271064,52203190,82070939,and 22005265);Key Research and Development Project of Zhejiang Province(Grant number 2020C03035);Postdoctoral Science Foundation of China(Grant number 2020TQ0261);Fundamental Research Funds for the Central Universities(Grant number 2021FZZX003-01-03).

摘　　要：Posterior capsule opacification(PCO)is the most common long-term postoperative complication of cataract surgery,leading to secondary vision loss.Optimized intraocular lens(IOL)structure and appropriate pharmacological intervention,which provides physical barriers and biological inhibition,respectively,can block the migration,proliferation,and epithelial-mesenchymal transition(EMT)of lens epithelial cells(LECs)for PCO prophylaxis.Herein,a novel indomethacin-eluting IOL(INDOM-IOL)with an optimized sharper edge and a sustained drug release behavior was developed for PCO prevention.Indomethacin(INDOM),an ophthalmic non-steroidal anti-inflammatory drug(NSAID)used for postoperative ocular inflammation,was demonstrated to not only be able to suppress cell migration and down-regulate the expression of cyclooxygenase-2(COX-2)and EMT markers,including alpha-smooth muscle actin(α-SMA)and cyclin D1,but also promote the autophagy activation in LECs.Additionally,autophagy was also verified to be a potential therapeutic target for the down-regulation of EMT in LECs.The novel IOL,serving as a drug delivery platform,could carry an adjustable dose of hydrophobic indomethacin with sustained drug release ability for more than 28 days.In the rabbit PCO model,the indomethacin-eluting IOL showed excellent anti-inflammatory and anti-PCO effects.In summary,indomethacin is an effective pharmacological intervention in PCO prophylaxis,and the novel IOL we developed prevented PCO in vivo under its sustained indomethacin release property,which provided a promising approach for PCO prophylaxis in clinical application.

关 键 词：Posterior capsule opacification INDOMETHACIN AUTOPHAGY Drug-eluting IOLs Epithelial-mesenchymal transition 

分 类 号：R776.1[医药卫生—眼科]