SRPK1 inhibition modulates VEGF splicing to reduce pathological neovascularisation in a rat model of Retinopathy of Prematurity

PURPOSE. We tested the hypothesis that recombinant human VEGF-A165b and the serine arginine protein kinase (SRPK) inhibitor, SRPIN340, which controls splicing of the VEGF-A pre-mRNA, prevent neovascularisation in a rodent model of retinopathy of prematurity (ROP). METHODS. In the 50/10 oxygen-induced retinopathy (50/10 OIR) model that exposes newborn rats to repeated cycles of 24 h of 50% oxygen alternating with 24 h of 10% oxygen, pups received intraocular injections of SRPIN340, vehicle, VEGF165b, anti-VEGF antibody or saline. Wholemounts of retinas were prepared for isolectin immunohistochemistry, and pre-retinal or intravitreal neovascularisation (PRNV) determined by clock hour analysis. RESULTS. The anti-VEGF antibody (p