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Nat Commun ; 13(1): 2796, 2022 05 19.
Article in English | MEDLINE | ID: mdl-35589753

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.


Subject(s)
NF-E2-Related Factor 2 , Retinal Pigment Epithelium , Animals , Cell Line , Cell Movement , Cicatrix/metabolism , Epithelial-Mesenchymal Transition , NF-E2-Related Factor 2/genetics , NF-E2-Related Factor 2/metabolism , Polymers/metabolism , Rabbits , Retinal Pigment Epithelium/metabolism
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