The SRPK1 inhibitor SPHINX31 prevents increased retinal permeability in a rodent model of diabetes

Purpose In diabetic retinopathy (DR) microvascular damage results from ischaemia driven production of pro‐angiogenic vascular endothelial growth factor (VEGF) inducing angiogenesis and increased permeability in the retina. Small molecule inhibitors of serine‐rich protein kinase‐1 (SRPK1), with good penetration properties to the retina, have been shown to inhibit choroidal neovascularisation in mice as eye drops by decreasing pro‐angiogenic and increasing anti‐angiogenic VEGF isoforms. SRPK1 inhibitors such as SPHINX31 may therefore switch splicing in DR and prevent increased vascular permeability. Methods FFA was performed in Norway Brown rats on day 0 and 7, using the Micron IV retinal microscope (Phoenix Research). Animals received twice daily topical eye drops with eye formulation only control buffer (n = 5) or SPHINX31 (200 μg/ml, n = 6). On day 1 animals received a single dose of streptozotocin (50 mg/kg, i.p.) to induce type I diabetes and maintained for 1 week without insulin. The ratio of interstitial to vascular fluorescence was calculated and plotted against time to determine an estimate of permeability. Results Retinal permeability (12.67 ± 1.09 × 10−4 cms−1) was shown to significantly increase (p