Pharmacological depletion of pericytes induces diabetic retinopathy-like abnormal blood vessels in neonatal rat retina.

Diabetic retinopathy is a major ocular complication associated with diabetes mellitus. Pericyte loss is a hallmark of diabetic retinopathy. The platelet-derived growth factor (PDGF)-B-PDGF receptor-β (PDGFRβ) signaling pathway plays an important role in the proliferation and migration of pericytes. Imatinib, an antineoplastic drug primarily used to treat chronic myelogenous leukemia, inhibits the PDGFRβ tyrosine kinase. In this study, we aimed to determine the time-course of pathological changes in the retinal vasculature following pharmacological depletion of pericytes with imatinib. Rats were injected with imatinib once daily for 1, 2, or 4 days starting on postnatal day (P) 4. The distribution of endothelial cells and pericytes in the retina was assessed at P4, P5, P6, P8, and P11. Single and multiple injections of imatinib (100 mg/kg) significantly decreased the pericyte coverage within the retinal capillaries on the day after the completion of each injection protocol. After pericyte coverage decreased, endothelial cell degeneration and microaneurysm formation were initiated. Following the elimination of the inhibitory effect of imatinib on the PDGFRβ signaling pathway, the pericyte coverage returned to control levels but structural abnormalities of the retinal vasculature with microaneurysms and dense capillaries were observed. Vascular pathological features are similar to those of the early clinical manifestations of diabetic retinopathy. Therefore, these rats could serve as animal models to study the mechanisms underlying the pathological changes that occur after pericyte loss in diabetic retinopathy.