Abstract
Purpose :
One of the most common causes of vision loss after retinal surgery is the formation of scar tissue on, in or under the retina, which can result in proliferative vitreoretinopathy (PVR). The current standard practice involves surgical removal of scar tissue, which carries intrinsic risk. Even if PVR is successfully treated by surgery, vision impairment could still result, and hence there is an urgent need to find alternative non-surgical solutions for PVR prevention.
Methods :
Thermogelling polymer, composed of poly(ethylene glycol) (PEG), poly(propylene glycol) (PPG) and poly(ε-caprolactone) (PCL), referred to as poly(CEP), was synthesized. A surgically induced rabbit model of PVR was used to validate poly(CEP)’s efficacy in preventing PVR, in comparison to Sulfur Hexafluoride (SF6). The polymer-cell interactions and the effect on scarring were further investigated in an in vitro model of PVR using human embryonic stem cell-derived retinal pigment epithelial (ES-RPE) cells. Cellular assays to study poly(CEP)’s effects on hyper-proliferation and increased migratory capacity of RPE cells, were conducted. Poly(CEP) internalization was observed using flow cytometry. Key epithelial-mesenchymal transition (EMT) markers were analyzed at both mRNA and protein level.
Results :
Poly(CEP) prevented fibrosis, scarring and tractional retinal detachment in the rabbit model of PVR, in addition to acting as an effective vitreous tamponade. Poly(CEP) at 1wt%, in its micellar form and in a concentration-dependent manner, completely inhibited the formation of contractile fibrocellular membranes in the in vitro model of PVR. Furthermore, at the same concentration of 1wt%, poly(CEP) showed the highest suppression of proliferation and migration of RPE cells. Poly(CEP) exerted this anti-scarring property after internalization and through the modulation of EMT-related transcription factor genes.
Conclusions :
In this work, we show that a thermogelling polymer prevents retinal scarring in a pre-clinical rabbit model of PVR. This is mediated via a polymer-induced impairment of EMT, which results in suppression of RPE cell proliferation and migration. This is the first report wherein a synthetic polymeric material, without the use of any small molecule therapeutics, is shown to inhibit EMT and prevent retinal scarring. This study highlights the potential of the next generation of nanomedicine whereby small molecule drugs are no longer required.
This is a 2021 ARVO Annual Meeting abstract.