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.

Customized strategies for high-yield purification of retinal pigment epithelial cells differentiated from different stem cell sources

“…RPE was generated from skin-iPSCs (asF5 and HDFa) and ESCs (H9 and H1) sources using a 16-day directed differentiation protocol 12 , 20 . After 16 days of differentiation, the cells were allowed to further mature and develop pigmentation in RPE maintenance medium for additional 15–20 days.…”

“…To further ensure the purity of the RPE, we looked for the presence of other markers specific to non-RPE cell types such as pluripotent ( LIN28 and OCT4 ), mesenchymal cells (Fibronectin and SNAIL2 ) and endodermal cells ( SOX17 ) by qPCR and found them to be absent in the purified cells (Fig. S2 ) 20 , 22 . This further confirms the purity of HDFa-RPE cells, consistent with the PMEL17 flow cytometry results.…”

“…The iPSC lines were maintained feeder-free in mTeSR1 (StemCell Technologies 85850). Human ESCs (H1 and H9) were cultured as described previously 20 .…”

“…The iPSC (HDFa and asF5) and ESC (H1 and H9) were differentiated into RPE using published protocol with minor modifications 12 , 20 . For differentiation, the stem cells were grown to 90% confluency in mTeSR1 on six-well culture plates coated with Matrigel (Corning 354230).…”

Polymeric biomaterials in the treatment of posterior segment diseases

“…More importantly, it offers insight into how synthetic polymeric materials no longer function merely as inert drug carriers and challenges the conventional belief that a small molecule (drug) is always required to achieve a therapeutic effect at a cellular level. It lays the foundation for next generation nanomedicine, whereby polymers alone can be used to elicit specific biological responses ( 13 ).…”