COX17 Attenuates Diabetes-Associated Retinal Injury by Improving Mitochondrial Function

IF 2.5 4区医学 Q2 Medicine

Clinical and Experimental Pharmacology and Physiology Pub Date : 2025-12-05 DOI:10.1111/1440-1681.70098

Hai-Yan Lian, Zhen-De Deng, Ming Yan, Zhen Huang, Ya Ye, Yan-Ping Song

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引用次数: 0

Abstract

Purpose

Diabetic retinopathy (DR), a common complication of diabetes, is a leading cause of blindness globally. Cytochrome C oxidase copper chaperone (COX17) is important for Cytochrome C oxidase assembly, and COX17 overexpression is reported to improve mitochondrial function in renal tissue. This study aimed to explore whether COX17 alleviated DR by regulating mitochondrial function.

Methods

Diabetes was induced in rats by a single intraperitoneal injection of 65 mg/kg streptozotocin (STZ). Overexpression of COX17 was performed by infection of adeno-associated virus into the vitreous body of rats 2 weeks after STZ injection. Human retinal microvascular endothelial cells (HRMECs) were cultured with high-glucose (HG) medium (20 mM d-glucose). Immunofluorescence assay, enzymatic histochemistry assay, CCK-8 assay, DCFH-DA staining, flow cytometry, western blot, and real-time PCR were performed.

Results

COX17 expression was decreased in the retinal tissues of diabetic rats and HG-stimulated HRMECs. COX17 overexpression alleviated retinal neovascularisation and increased retinal thickness in diabetic rats. COX17 overexpression decreased ROS and apoptosis and increased Cytochrome C oxidase activity, mtDNA copy number, ATP content, and mitochondrial membrane potential (MMP) in both the retinal tissues of diabetic rats and HG-induced HRMECs. Overexpression of COX17 effectively reduced cell apoptosis and increased cell viability. Overexpression of COX17 increased mtDNA in HG-induced HRMECs.

Conclusions

Overall, our study suggested that COX17 overexpression exerted protective effects in the retinas of diabetic rats and in HRMECs by stabilising mitochondrial function.

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COX17通过改善线粒体功能减轻糖尿病相关视网膜损伤

目的：糖尿病视网膜病变（DR）是糖尿病的一种常见并发症，是全球失明的主要原因。细胞色素C氧化酶铜伴侣（COX17）在细胞色素C氧化酶组装中起重要作用，据报道，过表达COX17可改善肾组织线粒体功能。本研究旨在探讨COX17是否通过调节线粒体功能减轻DR。方法：单次腹腔注射链脲佐菌素（STZ） 65 mg/kg诱导大鼠糖尿病。注射STZ 2周后，用腺相关病毒感染大鼠玻璃体实现COX17的过表达。采用高糖（HG）培养基（20 mM d-葡萄糖）培养人视网膜微血管内皮细胞（HRMECs）。免疫荧光、酶组织化学、CCK-8、DCFH-DA染色、流式细胞术、western blot、real-time PCR检测。结果：COX17在糖尿病大鼠视网膜组织和hg刺激的hrmec中表达降低。COX17过表达可减轻糖尿病大鼠视网膜新生血管的形成和视网膜厚度的增加。在糖尿病大鼠和hg诱导的HRMECs视网膜组织中，过表达COX17可降低ROS和凋亡，增加细胞色素C氧化酶活性、mtDNA拷贝数、ATP含量和线粒体膜电位（MMP）。过表达COX17可有效减少细胞凋亡，提高细胞活力。在hg诱导的hrmec中，过表达COX17增加了mtDNA。结论：总的来说，我们的研究表明，cox - 17过表达通过稳定线粒体功能在糖尿病大鼠和hrmec视网膜中发挥保护作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical and Experimental Pharmacology and Physiology 医学-生理学

CiteScore

6.20

自引率

0.00%

发文量

128

审稿时长

6 months

期刊介绍： Clinical and Experimental Pharmacology and Physiology is an international journal founded in 1974 by Mike Rand, Austin Doyle, John Coghlan and Paul Korner. Our focus is new frontiers in physiology and pharmacology, emphasizing the translation of basic research to clinical practice. We publish original articles, invited reviews and our exciting, cutting-edge Frontiers-in-Research series’.

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原料信息

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HRP-labelled goat anti-rabbit IgG

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2 × Taq PCR MasterMix

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Cytochrome C oxidase assay kit

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