GLP-1RA 通过 GLP-1R-ROCK-p-MLC 信号通路改善糖尿病视网膜病变。

GLP-1 RA Improves Diabetic Retinopathy by Protecting the Blood-Retinal Barrier through GLP-1R-ROCK-p-MLC Signaling Pathway.

机构信息

Department of Laboratory, The First Affiliated Hospital of Guangxi Medical University, No. 22 Shuangyong Road, Nanning, 530021 Guangxi, China.

Department of Endocrinology, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, 530021 Guangxi, China.

出版信息

J Diabetes Res. 2022 Nov 3;2022:1861940. doi: 10.1155/2022/1861940. eCollection 2022.

BACKGROUND

GLP-1 receptor agonists (GLP-1RA) are common clinical agents that are clinically protective against diabetic complications, such as diabetic retinopathy (DR). Previous studies have shown that the RhoA/ROCK pathway plays an important role in the development of DR. However, the specific mechanism of action between GLP-1RA and DR remains unclear. The aim of this study was thus to investigate the main mechanism involved in the protective effect of GLP-1RA on DR.

METHODS

Type 2 diabetic mice were fed a high-sugar, high-fat diet. Changes in the retinal structure were observed via HE staining and transmission electron microscopy. The expression of retinal GLP-1R, blood-retinal barrier- (BRB-) related proteins, inflammatory factors, and related pathway proteins were studied via Western blot or immunohistochemistry/immunofluorescence analysis.

RESULTS

GLP-1RA treatment reduced the blood glucose and lipid levels as well as the body weight of the diabetic mice while also improving retinal thickness, morphology, and vascular ultrastructure. Moreover, restored GLP-1R expression, increased Occludin and ZO-1 levels, and decreased albumin expression led to reduced retinal leakage and improved the BRB by inhibiting the RhoA/ROCK pathway.

CONCLUSIONS

We found that the protective effect of GLP-1RA on the retina may be realized through the GLP-1R-ROCK-p-MLC signaling pathway.

背景

GLP-1 受体激动剂（GLP-1RA）是常见的临床药物，对糖尿病并发症具有临床保护作用，如糖尿病视网膜病变（DR）。先前的研究表明，RhoA/ROCK 通路在 DR 的发展中起着重要作用。然而，GLP-1RA 与 DR 之间的具体作用机制尚不清楚。因此，本研究旨在探讨 GLP-1RA 对 DR 保护作用的主要机制。