A bio-functional polymer that prevents retinal scarring through modulation of NRF2 signalling pathway

Bhav Harshad Parikh, Zengping Liu, Paul Blakeley, Qianyu Lin, Malay Singh, Jun Yi Ong, Kim Han Ho, Joel Weijia Lai, Hanumakumar Bogireddi, Kim Chi Tran, Jason Y.C. Lim, Kun Xue, Abdurrahmaan Al-Mubaarak, Binxia Yang, R. Sowmiya, Kakkad Regha, Daniel Soo Lin Wong, Queenie Shu Woon Tan, Zhongxing Zhang, Anand D. JeyasekharanVeluchamy Amutha Barathi, Weimiao Yu, Kang Hao Cheong, Timothy A. Blenkinsop, Walter Hunziker, Gopal Lingam, Xian Jun Loh, Xinyi Su

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

One common cause of vision loss after retinal detachment surgery is the formation of proliferative and contractile fibrocellular membranes. This aberrant wound healing process is mediated by epithelial-mesenchymal transition (EMT) and hyper-proliferation of retinal pigment epithelial (RPE) cells. Current treatment relies primarily on surgical removal of these membranes. Here, we demonstrate that a bio-functional polymer by itself is able to prevent retinal scarring in an experimental rabbit model of proliferative vitreoretinopathy. This is mediated primarily via clathrin-dependent internalisation of polymeric micelles, downstream suppression of canonical EMT transcription factors, reduction of RPE cell hyper-proliferation and migration. Nuclear factor erythroid 2–related factor 2 signalling pathway was identified in a genome-wide transcriptomic profiling as a key sensor and effector. This study highlights the potential of using synthetic bio-functional polymer to modulate RPE cellular behaviour and offers a potential therapy for retinal scarring prevention.

Original languageEnglish
Article number2796
JournalNature Communications
Volume13
Issue number1
DOIs
StatePublished - Dec 2022

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