Affiliation:
1. Affiliated Hospital of Hangzhou Normal University, Hangzhou Institute of Cardiovascular Diseases, Zhejiang Key Laboratory of Medical Epigenetics, Hangzhou Normal University, Zhejiang Key Laboratory for Research in Assessment of Cognitive Impairments, Hangzhou, 310015, China
2. Hangzhou Lin'an Fourth People's Hospital, Hangzhou 311321, China
3. Hangzhou Normal University, Hangzhou, 311121, China
Abstract
Background Diabetic retinopathy (DR) frequently results in compromised visual function, with hyperglycemia-induced disruption of the blood-retinal barrier (BRB) through various pathways as a critical mechanism. Existing DR treatments fail to address early and potentially reversible microvascular alterations. This study examined the effects of empagliflozin (EMPA), a selective Sodium-glucose transporter 2 (SGLT2) inhibitor, on the retina of db/db mice. The objective of this study is to investigate the potential role of EMPA in the prevention and delay of DR. Methods db/db mice were randomly assigned to either the EMPA treatment group (db/db + Emp) or the model group (db/db), while C57 mice served as the normal control group (C57). Mice in the db/db + Emp group received EMPA for eight weeks. Body weight, fasting blood glucose (FBG), and blood VEGF were subsequently measured in all mice, along with the detection of specific inflammatory factors and BRB proteins in the retina. Retinal SGLT2 protein expression was compared using immunohistochemical analysis, and BRB structural changes were observed via electron microscopy. Results EMPA reduced FBG, blood VEGF, and retinal inflammatory factors TNF-α, IL-6, and VEGF levels in the eye tissues of db/db mice. EMPA also increased Claudin-1, Occludin-1, and ZO-1 levels while decreasing ICAM-1 and Fibronectin, thereby preserving BRB function in db/db mice. Immunohistochemistry revealed that EMPA reduced SGLT2 expression in the retina of diabetic mice, and electron microscopy demonstrated that EMPA diminished tight junction damage between retinal vascular endothelial cells and prevented retinal vascular basement membrane thickening in diabetic mice. Conclusion EMPA mitigates inflammation and preserves BRB structure and function, suggesting that it may prevent DR or serve as an effective early treatment for DR.
Funder
Medical and Technology Project of Zhejiang Province
Zhejiang Kangenbei Hospital Management Soft Science Research Project
Clinical Research Fund of Zhejiang Medical Association
Hospital Fund of Affiliated Hospital of Hangzhou Normal University
the National Natural Science Foundation of China
Hangzhou science and Technology Bureau fund