Dapagliflozin ameliorated retinal vascular permeability in diabetic retinopathy rats by suppressing inflammatory factors

• Published in: Journal of diabetes and its complications 2024-03, Vol.38 (3), p.108631-108631, Article 108631
• Main Authors: Xu, Chengye, Li, Hongxue, Xu, Qian, Zhao, Kangqi, Hao, Ming, Lin, Wenjian, Ma, Xuefei, Gao, Xinyuan, Kuang, Hongyu
• Format: Article
• Language: English
• Subjects: Antibodies; Antidiabetics; Bioavailability; Dapagliflozin; Diabetes; Diabetic retinopathy; Glucose; Homeostasis; Inflammation; Inflammatory factors; Insulin resistance; Laboratory animals; Peptides; Permeability; Plasma; Proteins; Retinal vascular permeability; SGLT-2i
• ISSN: 1056-8727; 1873-460X
• DOI: 10.1016/j.jdiacomp.2023.108631

Diabetic retinopathy is a common microvascular complication of diabetes and one of the major causes of blindness in the working-age population. Emerging evidence has elucidated that inflammation drives the key mechanism of diabetes-mediated retinal disturbance. As a new therapeutic drug targeting diabetes, whether dapagliflozin could improve vascular permeability from the perspective of anti-inflammatory effect need to be further explored. Type 2 diabetic retinopathy rat model was established and confirmed by fundus fluorescein angiography (FFA). ELISA detected level of plasma inflammatory factors and C-peptide. HE staining, immunohistochemistry and western blot detected histopathology changes of retina, expression of retinal inflammatory factors and tight junction proteins. Dapagliflozin exhibited hypoglycemic effect comparable to insulin, but did not affect body weight. By inhibiting expression of inflammatory factors (NLRP3, Caspase-1, IL-18, NF-κB) in diabetic retina and plasma, dapagliflozin reduced damage of retinal tight junction proteins and improved retinal vascular permeability. The anti-inflammatory effect of dapagliflozin was superior to insulin. Dapagliflozin improved retinal vascular permeability by reducing diabetic retinal and plasma inflammatory factors. The anti-inflammatory mechanism of dapagliflozin is independent of hypoglycemic effect and superior to insulin. •Dapagliflozin ameliorated vascular permeability by suppressing expression of inflammatory cytokines in retina and plasma.