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Translocator protein (18 kDa) (Tspo) in the retina and implications for ocular diseases
Progress in Retinal and Eye Research ( IF 17.8 ) Pub Date : 2024-03-01 , DOI: 10.1016/j.preteyeres.2024.101249
Mandy Hector , Thomas Langmann , Anne Wolf

Translocator protein (18 kDa) (Tspo), formerly known as peripheral benzodiazepine receptor is a highly conserved transmembrane protein primarily located in the outer mitochondrial membrane. In the central nervous system (CNS), especially in glia cells, Tspo is upregulated upon inflammation. Consequently, Tspo was used as a tool for diagnostic imaging of neuroinflammation in the brain and as a potential therapeutic target. Several synthetic Tspo ligands have been explored as immunomodulatory and neuroprotective therapy approaches. Although the function of Tspo and how its ligands exert these beneficial effects is not fully clear, it became a research topic of interest, especially in ocular diseases in the past few years. This review summarizes state-of-the-art knowledge of Tspo expression and its proposed functions in different cells of the retina including microglia, retinal pigment epithelium and Müller cells. Tspo is involved in cytokine signaling, oxidative stress and reactive oxygen species production, calcium signaling, neurosteroid synthesis, energy metabolism, and cholesterol efflux. We also highlight recent developments in preclinical models targeting Tspo and summarize the relevance of Tspo biology for ocular and retinal diseases. We conclude that glial upregulation of Tspo in different ocular pathologies and the use of Tspo ligands as promising therapeutic approaches in preclinical studies underline the importance of Tspo as a potential disease-modifying protein.

中文翻译:

视网膜中的易位蛋白 (18 kDa) (Tspo) 及其对眼部疾病的影响

易位蛋白 (18 kDa) (Tspo),以前称为外周苯二氮卓受体,是一种高度保守的跨膜蛋白,主要位于线粒体外膜。在中枢神经系统 (CNS) 中,特别是在神经胶质细胞中,Tspo 在炎症时上调。因此,Tspo 被用作大脑神经炎症诊断成像的工具和潜在的治疗靶点。几种合成的 Tspo 配体已被探索作为免疫调节和神经保护治疗方法。尽管Tspo的功能及其配体如何发挥这些有益作用尚不完全清楚,但它成为了人们感兴趣的研究课题,特别是在过去几年的眼部疾病方面。这篇综述总结了 Tspo 表达的最新知识及其在视网膜不同细胞(包括小胶质细胞、视网膜色素上皮和 Müller 细胞)中的功能。 Tspo 参与细胞因子信号传导、氧化应激和活性氧产生、钙信号传导、神经类固醇合成、能量代谢和胆固醇流出。我们还重点介绍了针对 Tspo 的临床前模型的最新进展,并总结了 Tspo 生物学与眼部和视网膜疾病的相关性。我们得出的结论是,不同眼部病理中 Tspo 的神经胶质上调以及 Tspo 配体在临床前研究中作为有前景的治疗方法的使用强调了 Tspo 作为潜在疾病缓解蛋白的重要性。
更新日期:2024-03-01
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