Journal
FASEB JOURNAL
Volume 32, Issue 5, Pages 2324-2338Publisher
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.201700570RR
Keywords
diabetic retinopathy; pericyte apoptosis; vascular leakage; tight junction protein
Categories
Funding
- National Research Foundation of Korea - Korean government [2014R1A2A1A11050981, 2012R1A5A2A44671346]
- Seoul National University Hospital Research Fund [0420160230]
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available