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, Sowmiya R, Kakkad Regha, Daniel Soo Lin Wong, Queenie Shu Woon Tan, Zhongxing Zhang, Anand D. Jeyasekharan, Veluchamy Amutha Barathi, Weimiao Yu, Kang Hao Cheong, Timothy A. Blenkinsop, Walter Hunziker, Gopal Lingam, Xian Jun Loh () and Xinyi Su ()
Additional contact information
Bhav Harshad Parikh: Agency for Science, Technology and Research (A*STAR)
Zengping Liu: Agency for Science, Technology and Research (A*STAR)
Paul Blakeley: Yong Loo Lin School of Medicine, National University of Singapore
Qianyu Lin: Agency for Science, Technology and Research (A*STAR)
Malay Singh: Agency for Science, Technology and Research (A*STAR)
Jun Yi Ong: Agency for Science, Technology and Research (A*STAR)
Kim Han Ho: Agency for Science, Technology and Research (A*STAR)
Joel Weijia Lai: Singapore University of Technology and Design (SUTD)
Hanumakumar Bogireddi: Yong Loo Lin School of Medicine, National University of Singapore
Kim Chi Tran: Yong Loo Lin School of Medicine, National University of Singapore
Jason Y. C. Lim: Agency for Science, Technology and Research (A*STAR)
Kun Xue: Agency for Science, Technology and Research (A*STAR)
Abdurrahmaan Al-Mubaarak: Yong Loo Lin School of Medicine, National University of Singapore
Binxia Yang: Agency for Science, Technology and Research (A*STAR)
Sowmiya R: Agency for Science, Technology and Research (A*STAR)
Kakkad Regha: Agency for Science, Technology and Research (A*STAR)
Daniel Soo Lin Wong: Yong Loo Lin School of Medicine, National University of Singapore
Queenie Shu Woon Tan: Agency for Science, Technology and Research (A*STAR)
Zhongxing Zhang: Agency for Science, Technology and Research (A*STAR)
Anand D. Jeyasekharan: National University of Singapore
Veluchamy Amutha Barathi: Yong Loo Lin School of Medicine, National University of Singapore
Weimiao Yu: Agency for Science, Technology and Research (A*STAR)
Kang Hao Cheong: Singapore University of Technology and Design (SUTD)
Timothy A. Blenkinsop: Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai
Walter Hunziker: Agency for Science, Technology and Research (A*STAR)
Gopal Lingam: Yong Loo Lin School of Medicine, National University of Singapore
Xian Jun Loh: Agency for Science, Technology and Research (A*STAR)
Xinyi Su: Agency for Science, Technology and Research (A*STAR)

Nature Communications, 2022, vol. 13, issue 1, 1-16

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-30474-6

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