The impact of sestrin2 on reactive oxygen species in diabetic retinopathy

• Published in: Cell biochemistry and function Vol. 42; no. 4; pp. e4024 - n/a
• Main Authors: Yang, Xueli, Wu, Xiaoli
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.06.2024
• Subjects: Animals; Cell proliferation; Cell Proliferation - drug effects; Cells, Cultured; Damage; Diabetes; Diabetes mellitus; Diabetes Mellitus, Experimental - metabolism; Diabetes Mellitus, Experimental - pathology; Diabetic retinopathy; Diabetic Retinopathy - metabolism; Diabetic Retinopathy - pathology; Ependymoglial Cells - drug effects; Ependymoglial Cells - metabolism; Ependymoglial Cells - pathology; Glia; Glial cells; glial fibrillary acidic protein; Glucose; Glucose - metabolism; Glutamate-ammonia ligase; Glutamine; glutamine synthetase; Heme oxygenase (decyclizing); Inflammation; Male; Microvasculature; Mueller cells; Müller cell; NF-E2-Related Factor 2 - metabolism; oxidative stress; Oxygen; Pathogenesis; Peroxidases - metabolism; Protected species; Rats; Rats, Sprague-Dawley; Reactive oxygen species; Reactive Oxygen Species - metabolism; Retina; Retinopathy; sestrin2; Sestrins; Signal transduction; Signal Transduction - drug effects; Müller cell; glutamine synthetase; glial fibrillary acidic protein; oxidative stress; sestrin2
• ISSN: 0263-6484; 1099-0844; 1099-0844
• DOI: 10.1002/cbf.4024

Diabetic retinopathy (DR) is a significant complication of diabetes that often leads to blindness, impacting Müller cells, the primary retinal macroglia involved in DR pathogenesis. Reactive oxygen species (ROS) play a crucial role in the development of DR. The objective of this study was to investigate the involvement of sestrin2 in DR using a high‐glucose (HG)‐induced Müller cell model and assessing cell proliferation with 5‐ethynyl‐2‐deoxyuridine (EdU) labeling. Following this, sestrin2 was upregulated in Müller cells to investigate its effects on ROS, tube formation, and inflammation both in vitro and in vivo, as well as its interaction with the nuclear factor erythroid2‐related factor 2 (Nrf2) signaling pathway. The findings demonstrated a gradual increase in the number of EdU‐positive cells over time, with a subsequent decrease after 72 h of exposure to high glucose levels. Additionally, the expression of sestrin2 exhibited a progressive increase over time, followed by a decrease at 72 h. The rh‐sestrin2 treatment suppressed the injury of Müller cells, decreased ROS level, and inhibited the tube formation. Rh‐sestrin2 treatment enhanced the expression of sestrin2, Nrf2, heme oxygenase‐1 (HO‐1), and glutamine synthetase (GS); however, the ML385 treatment reversed the protective effect of rh‐sestrin2. Finally, we evaluated the effect of sestrin2 in a DR rat model. Sestrin2 overexpression treatment improved the pathological injury of retina and attenuated the oxidative damage and inflammatory reaction. Our results highlighted the inhibitory effect of sestrin2 in the damage of retina, thus presenting a novel therapeutic sight for DR. Significance statement Diabetic retinopathy (DR) is a microvascular complication associated with diabetes. Müller cells serve as the basically glial cells within the retina. Alterations in the retinal environment can impact the functionality and well‐being of Müller cells, subsequently affecting the overall health of the retina. Sestrin2, a stress‐induced metabolic protein with high conservation, has the ability to suppress oxygen species and offer cellular protection against diverse detrimental stimuli. Consequently, it is necessary to confirm the impact of sestrin2 on the Müller cells in the context of DR.