POLYMERIC MICELLES AS A NOVEL APPROACH IN THE PREVENTION OF RETINAL SCARRING

Abstract

One common cause of vision loss after retinal detachment surgery is the formation of scar membranes. This aberrant retinal scarring, termed proliferative vitreoretinopathy (PVR), is mediated by epithelial-mesenchymal transition (EMT) and hyper-proliferation of retinal pigmental epithelial (RPE) cells. Current treatment options are limited to surgical removal of these membranes, with no approved pharmacologic agents, and poor success rates. Here, it is demonstrated that a polymer alone is able to prevent retinal scarring in a rabbit model of PVR. This is mediated via internalisation of the polymeric micelles, suppression of EMT transcription factors, and reduction of RPE hyper-proliferation and migration. Nuclear factor erythroid 2-related factor 2 (NRF2) signalling pathway was identified in a genome-wide transcriptomic profiling as a key sensor and effector, whose activation was sufficient to prevent scarring. This study highlights the potential of using synthetic polymer to modulate cellular behaviour and offers a potentially novel therapy for retinal scarring.