Endostatin Inhibits Blood-Retinal Barrier Breakdown in Diabetic Rats by Increasing the Expression of ICAM-1 and VCAM-1 and Decreasing the Expression of VEGF.

Jinhua Zhou,Zhenggao Xie,Chang Gu

doi:10.1155/2022/5105866

Jinhua Zhou, Zhenggao Xie + Show 1 more

Open Access

https://doi.org/10.1155/2022/5105866

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Abstract

Endostatin has become the strongest endogenous angiogenesis inhibitor due to suppressing VEGF expression. The purpose of this study was to assess the impact of endostatin on the blood-retinal barrier (BRB) in diabetic rats. SD rats were induced to develop diabetes by streptozotocin, and endostatin was administrated by intravitreal injection. The body weight, the level of blood glucose, the expressions of C-reactive protein (CRP), adhesion molecules intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), junction proteins (occludin, claudin-5, and zonula occluden-1), and VEGF were measured in rats' retinas of diabetes. The BRB breakdown was evaluated using Evans blue. The level of CRP and adhesion molecules (ICAM-1 and VCAM-1) was increased in retinas of diabetic rats, while endostatin significantly inhibited the upregulation of these. Diabetes increased the BRB permeability and retinal thickness. Diabetes also decreased the levels of occludin, claudin-5, and ZO-1 in retinals. These changes were inhibited by endostatin treatment. Upregulation of vascular endothelial growth factor (VEGF), transforming growth factor-β (TGF-β), and protein kinase C- (PKC-) β2 was also reversed by endostatin in retinas of diabetic rats. Endostatin provides protection against diabetic retinopathy, which may involve its barrier-enhancing effects.

Highlights

Diabetic retinopathy is a common and specific microvascular complication of diabetes, and it is still the main cause of blindness prevention among working-aged population [1]
The main signs of nonproliferative diabetic retinopathy stage are the disruption of the blood-retinal barrier (BRB) and exudation increased, resulting in ischemia and hypoxia [19,20,21]
The tight junctions of the retinal vascular endothelial cells are the basis of the structure and function of BRB, which is mainly composed of transmembrane proteins, cytoplasmic attachment proteins, and cytoskeletal proteins, regulating the permeability of BRB [23]

Summary

Introduction

Diabetic retinopathy is a common and specific microvascular complication of diabetes, and it is still the main cause of blindness prevention among working-aged population [1]. It was found in 1/3 of diabetic patients and is associated with increased risk of life-threatening systemic vascular complications, including stroke, coronary heart disease, and heart failure. Its main pathological change is the destruction of blood-retinal barrier (BRB). Similar to the bloodbrain barrier, BRB selectively regulates the microenvironment of retinal nerve tissue, vascular permeability and balance, ion concentration, and transport metabolites [4]. BRB destruction is an important part of the pathogenesis of diabetic retinopathy, which can result in increased permeability to lipids and protein and mainly clinically manifested as microangioma, hemorrhage, hard exudation, and macular edema [1, 7]

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