beta-Adrenergic receptor agonists attenuate pericyte loss in diabetic retinas through Akt activation

Pericytes (PCs) are crucial in maintaining the quiescence of endothelial cells (ECs) and the integrity of EC tight junctions. Especially in diabetic retinopathy (DR), PC loss is one of the early pathologic changes in capillaries of diabetic retinas. Thus, preventing PC loss is beneficial for attenuating vision impairment in patients with DR. Although many studies have revealed the mechanism of PC loss in retinas, little is known about the mechanisms that increase PC survival. We focused on the effect of beta-adrenergic receptor agonists (beta-agonists) on PC loss in diabetic retinas. In this study, beta-agonists increased the cell viability of PCs by increasing PC survival and proliferation. Mechanistically, beta-agonist-induced protein kinase B activation in PCs reduced PC apoptosis in response to various stimuli. beta 2-agonists more potently increased PC survival than beta 1-agonists. beta 2-Agonist reduced vascular leakage and PC loss in retinas of mice with streptozotocin-induced diabetes. In cocultures of PCs and ECs, beta 2-agonists restored the altered permeability and ZO-1 expression in ECs induced by PC loss. We concluded that beta-agonists, especially beta 2-agonists, increase PC survival, thereby preventing diabetes-induced PC loss in retinas. These results provide a potential therapeutic benefit of beta-agonists for preventing PC loss in DR.