Translocator protein (18 kDa) (Tspo) in the retina and implications for ocular diseases

IF 18.6 1区 医学 Q1 OPHTHALMOLOGY Progress in Retinal and Eye Research Pub Date : 2024-03-01 DOI:10.1016/j.preteyeres.2024.101249
Mandy Hector , Thomas Langmann , Anne Wolf
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Abstract

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 in vivo 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.

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视网膜中的转运蛋白(18 kDa)(Tspo)及其对眼部疾病的影响。
转运蛋白(18 kDa)(Tspo),以前称为外周苯并二氮杂卓受体,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 被用作脑部神经炎症的体内成像诊断工具和潜在的治疗靶点。一些合成的 Tspo 配体已被探索用作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,但在过去几年中,它已成为一个备受关注的研究课题,尤其是在眼科疾病方面。本综述总结了有关 Tspo 在视网膜不同细胞(包括小胶质细胞、视网膜色素上皮细胞和 Müller 细胞)中的表达及其功能的最新知识。Tspo 参与细胞因子信号传导、氧化应激和活性氧生成、钙信号传导、神经类固醇合成、能量代谢和胆固醇外流。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。我们的结论是,Tspo 在不同眼部病变中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 作为一种潜在的疾病修饰蛋白的重要性。
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来源期刊
CiteScore
34.10
自引率
5.10%
发文量
78
期刊介绍: Progress in Retinal and Eye Research is a Reviews-only journal. By invitation, leading experts write on basic and clinical aspects of the eye in a style appealing to molecular biologists, neuroscientists and physiologists, as well as to vision researchers and ophthalmologists. The journal covers all aspects of eye research, including topics pertaining to the retina and pigment epithelial layer, cornea, tears, lacrimal glands, aqueous humour, iris, ciliary body, trabeculum, lens, vitreous humour and diseases such as dry-eye, inflammation, keratoconus, corneal dystrophy, glaucoma and cataract.
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