ScholarWorks@중앙대학교

초록

Diabetic retinopathy (DR) is one of the vascular complications associated with diabetes mellitus. Pericyte loss is an early characteristic phenomenon in DR. However, the mechanism by which pericyte apoptosis occurs in DR is not fully understood. We have focused on the increased STAT3 activation in diabetic retinas because STAT3 activation is associated with inflammation, and persistent chronic inflammation is closely related to retinal lesions. In this study, we demonstrated that STAT3 was activated by IFN-gamma and IL-6 that highly expressed in diabetic retinas. We identified TNF-alpha as a potent inducer of pericyte apoptosis in diabetic retinas from the gene expression analysis and found that STAT3 activation in microglia increased TNF-alpha expression in the diabetic retinas. We also demonstrated that increased TNF-alpha expression in microglia caused pericyte apoptosis through downregulating AKT/p70S6 kinase signaling. Moreover, we took advantage of mice lacking STAT3 in microglia and demonstrated that STAT3 ablation in microglia reduced the pericyte apoptosis and TNF-alpha expression in the diabetic retinas. These results suggest that STAT3 activation in microglia plays an important role in pericyte apoptosis in the diabetic retinas through increased TNF-alpha expression and provide STAT3 activation in microglia as a potential therapeutic target for preventing pericyte loss in DR. (C) 2022 Elsevier Inc. All rights reserved.

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