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

Nat Commun. 2022 May 19;13(1):2796. doi: 10.1038/s41467-022-30474-6.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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

Substances

  • NF-E2-Related Factor 2
  • Polymers