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 - 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 -