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眼部进行性血管病变中脂联素水平升高。

Excess adiponectin in eyes with progressive ocular vascular diseases.

机构信息

Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan.

出版信息

FASEB J. 2021 Feb;35(2):e21313. doi: 10.1096/fj.202001740RR.

Abstract

Anti-vascular endothelial growth factor (VEGF) therapies are now the first-line treatment for many ocular diseases, but some patients are non-responders to these therapies. The purpose of this study was to determine whether the level of adiponectin increased the pathogenesis of retinal edema and neovascularization in the retina of progressive ocular vascular diseases. We examined the role played by adiponectin in two types of cells and animal models which are retinal vein occlusion (RVO) and oxygen-induced retinopathy (OIR) mice. Our results showed that an injection of anti-adiponectin antibody ameliorated the retinal edema and ischemia through the depression of the expression level of VEGF-related factors and tight junction-related proteins in the retina of RVO mice. The intravitreal injection of anti-adiponectin antibody also decreased the degree of retinal neovascularization in an OIR mice. In addition, exposure of human retinal microvascular endothelial cells and human brain microvascular pericytes in culture to adiponectin increased both the vascular permeability and neovascularization through the increase of inflammatory factor and the dropout of the pericytes. These findings indicate that adiponectin plays a critical role in retinal edema and neovascularization, and adiponectin is a potential therapeutic target for the treatment of diabetic macular edema, proliferative diabetic retinopathy, and RVO.

摘要

抗血管内皮生长因子 (VEGF) 疗法现已成为许多眼部疾病的一线治疗方法,但有些患者对这些疗法无反应。本研究旨在确定脂联素水平是否会增加进行性眼部血管疾病的视网膜水肿和新生血管形成的发病机制。我们研究了脂联素在两种类型的细胞和动物模型(视网膜静脉阻塞(RVO)和氧诱导的视网膜病变(OIR)小鼠)中的作用。结果表明,在 RVO 小鼠中,注射抗脂联素抗体可通过抑制 VEGF 相关因子和紧密连接相关蛋白在视网膜中的表达水平来改善视网膜水肿和缺血。抗脂联素抗体的玻璃体内注射也可减少 OIR 小鼠的视网膜新生血管形成程度。此外,体外培养的人视网膜微血管内皮细胞和人脑微血管周细胞暴露于脂联素可通过增加炎症因子和周细胞脱落来增加血管通透性和新生血管形成。这些发现表明,脂联素在视网膜水肿和新生血管形成中起关键作用,脂联素是治疗糖尿病性黄斑水肿、增殖性糖尿病视网膜病变和 RVO 的潜在治疗靶点。

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