IL-1-dependent ncRNA-based-therapy approach to enhance the bioactivity of endothelial progenitor cells in ischemic retinopathy: a new vasoprotective strategy
Retinopathy of prematurity (ROP) is the leading cause of blindness in premature neonates. ROP is associated with inflammation largely mediated trough interleukin (IL-1), which triggers an initial critical phase of ocular vascular degeneration. ROP is also an excellent model of ischemic retinopathies in general. The formation of new blood vessels after tissue ischemia is not only restricted to local endothelial cell proliferation, but lately shown to involve endothelial progenitor cells (EPCs) capable of forming a neovascular network on their own. It has been reported that pathological conditions associated with inflammation impair EPC bioactivity, and this in turn curtails post-ischemic revascularization. However the precise mechanisms responsible for this phenomenon remain unknown. We hypothesize that specific targeting of IL-1-dependent regulating microRNAs can reverse EPC dysfunction in ROP, and thus overcome vascular degeneration. This project aims to study: 1) the epigenetic mechanisms underlying IL-1-induced EPC dysfunction, and 2) evaluate novel therapeutic approaches to protect the bioactivity of EPCs during ROP using rytvela, a new antagonist of IL-1 receptor (in development by Rytvel Biotech), and specific IL-1-dependent ncRNA-based therapy. Hence, novel EPC reprogramming resulting in interference of inflammatory adversities could protect ocular vascular development; this concept can also apply to other ischemic vasculopathies.