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. Jeyasekharan; Veluchamy Amutha Barathi; Weimiao Yu; Kang Hao Cheong; Timothy A. Blenkinsop; Walter Hunziker; Gopal Lingam; Xian Jun Loh; Xinyi Su

doi:10.1038/s41467-022-30474-6

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

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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 language	English
Article number	2796
Journal	Nature Communications
Volume	13
Issue number	1
DOIs	https://doi.org/10.1038/s41467-022-30474-6
State	Published - Dec 2022

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Parikh, B. H., Liu, Z., Blakeley, P., Lin, Q., Singh, M., Ong, J. Y., Ho, K. H., Lai, J. W., Bogireddi, H., Tran, K. C., Lim, J. Y. C., Xue, K., Al-Mubaarak, A., Yang, B., Sowmiya, R., Regha, K., Wong, D. S. L., Tan, Q. S. W., Zhang, Z., ... Su, X. (2022). A bio-functional polymer that prevents retinal scarring through modulation of NRF2 signalling pathway. Nature Communications, 13(1), Article 2796. https://doi.org/10.1038/s41467-022-30474-6

@article{72dcaf6378ee4ba189969a6bdd65bc97,

title = "A bio-functional polymer that prevents retinal scarring through modulation of NRF2 signalling pathway",

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.",

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

note = "Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = dec,

doi = "10.1038/s41467-022-30474-6",

language = "English",

volume = "13",

journal = "Nature Communications",

issn = "2041-1723",

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Parikh, BH, Liu, Z, Blakeley, P, Lin, Q, Singh, M, Ong, JY, Ho, KH, Lai, JW, Bogireddi, H, Tran, KC, Lim, JYC, Xue, K, Al-Mubaarak, A, Yang, B, Sowmiya, R, Regha, K, Wong, DSL, Tan, QSW, Zhang, Z, Jeyasekharan, AD, Barathi, VA, Yu, W, Cheong, KH, Blenkinsop, TA, Hunziker, W, Lingam, G, Loh, XJ & Su, X 2022, 'A bio-functional polymer that prevents retinal scarring through modulation of NRF2 signalling pathway', Nature Communications, vol. 13, no. 1, 2796. https://doi.org/10.1038/s41467-022-30474-6

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

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.

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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 -

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

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