TY - JOUR
T1 - A bio-functional polymer that prevents retinal scarring through modulation of NRF2 signalling pathway
AU - Parikh, Bhav Harshad
AU - Liu, Zengping
AU - Blakeley, Paul
AU - Lin, Qianyu
AU - Singh, Malay
AU - Ong, Jun Yi
AU - Ho, Kim Han
AU - Lai, Joel Weijia
AU - Bogireddi, Hanumakumar
AU - Tran, Kim Chi
AU - Lim, Jason Y.C.
AU - Xue, Kun
AU - Al-Mubaarak, Abdurrahmaan
AU - Yang, Binxia
AU - Sowmiya, R.
AU - Regha, Kakkad
AU - Wong, Daniel Soo Lin
AU - Tan, Queenie Shu Woon
AU - Zhang, Zhongxing
AU - Jeyasekharan, Anand D.
AU - Barathi, Veluchamy Amutha
AU - Yu, Weimiao
AU - Cheong, Kang Hao
AU - Blenkinsop, Timothy A.
AU - Hunziker, Walter
AU - Lingam, Gopal
AU - Loh, Xian Jun
AU - Su, Xinyi
N1 - Funding Information:
We would like to acknowledge the veterinary team at the Translational Pre-Clinical Model Platform (Singapore Eye Research Institute, Singapore) for providing support in rabbit surgery preparation and animal follow-up. We are thankful to Central Imaging Facility at Institute of Molecular and Cell Biology (IMCB) for providing microscope resources. We also thank Xavier Le Guezennec from Frederic Bard’s lab at IMCB for kindly sharing and assisting with the Incucyte® Live-Cell Analysis System. This work was supported by the National Research Foundation (NRF), Singapore, under its Competitive Research Programme (CRP) [NRF-CRP21-2018-00103] and Agency for Science, Technology and Research (A*STAR), Singapore, HMBS Domain under its Industry Alignment Fund Pre-Positioning Programme(IAF-PP) [H20/H7/a0/034] awarded to X.S.
Funding Information:
We would like to acknowledge the veterinary team at the Translational Pre-Clinical Model Platform (Singapore Eye Research Institute, Singapore) for providing support in rabbit surgery preparation and animal follow-up. We are thankful to Central Imaging Facility at Institute of Molecular and Cell Biology (IMCB) for providing microscope resources. We also thank Xavier Le Guezennec from Frederic Bard’s lab at IMCB for kindly sharing and assisting with the Incucyte® Live-Cell Analysis System. This work was supported by the National Research Foundation (NRF), Singapore, under its Competitive Research Programme (CRP) [NRF-CRP21-2018-00103] and Agency for Science, Technology and Research (A*STAR), Singapore, HMBS Domain under its Industry Alignment Fund Pre-Positioning Programme(IAF-PP) [H20/H7/a0/034] awarded to X.S.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85130317759&partnerID=8YFLogxK
U2 - 10.1038/s41467-022-30474-6
DO - 10.1038/s41467-022-30474-6
M3 - Article
C2 - 35589753
AN - SCOPUS:85130317759
SN - 2041-1723
VL - 13
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 2796
ER -