Lab for Retinal Cell Biology, Department of Ophthalmology, University of Zurich, Schlieren, Switzerland; Center for Integrative Human Physiology (ZIHP), University of Zurich, Zurich, Switzerland.
Lab for Retinal Cell Biology, Department of Ophthalmology, University of Zurich, Schlieren, Switzerland.
Exp Eye Res. 2019 Nov;188:107816. doi: 10.1016/j.exer.2019.107816. Epub 2019 Sep 25.
Translocator protein (18 kDa) (TSPO) is a mitochondrial protein expressed by reactive microglia and astrocytes at the site of neuronal injury. Although TSPO function has not been fully determined, synthetic TSPO ligands have beneficial effects on different pathologies of the central nervous system, including the retina. Here, we studied the pattern of Tspo expression in the aging human retina and in two mouse models of retinal degeneration. Using a newly generated Tspo-KO mouse, we investigated the impact of the lack of TSPO on retinal morphology, function and susceptibility to degeneration. We show that TSPO was expressed in both human and mouse retina and retinal pigment epithelium (RPE). Tspo was induced in the mouse retina upon degeneration, but constitutively expressed in the RPE. Similarly, TSPO expression levels in healthy human retina and RPE were not differentially regulated during aging. Tspo-KO mice had normal retinal morphology and function up to 48 weeks of age. Photoreceptor loss caused either by exposure to excessive light levels or by a mutation in the phosphodiesterase 6b gene was not affected by the absence of Tspo. The reactivity states of retinal mononuclear phagocytes following light-damage were comparable in Tspo-KO and control mice. Our data suggest that lack of endogenous TSPO does not directly influence the magnitude of photoreceptor degeneration or microglia activation in these two models of retinal degeneration. We therefore hypothesize that the interaction of TSPO with its ligands may be required to modulate disease progression.
转位蛋白（18 kDa）（TSPO）是一种线粒体蛋白，在神经元损伤部位由反应性小胶质细胞和星形胶质细胞表达。尽管 TSPO 的功能尚未完全确定，但合成的 TSPO 配体对中枢神经系统的不同病理状态，包括视网膜，具有有益的作用。在这里，我们研究了 Tspo 在衰老的人视网膜和两种视网膜变性的小鼠模型中的表达模式。使用新生成的 Tspo-KO 小鼠，我们研究了缺乏 TSPO 对视网膜形态、功能和易变性的影响。我们表明，TSPO 在人和小鼠的视网膜和视网膜色素上皮（RPE）中表达。Tspo 在小鼠视网膜变性时被诱导，但在 RPE 中持续表达。同样，健康人视网膜和 RPE 中 TSPO 的表达水平在衰老过程中没有差异调节。Tspo-KO 小鼠的视网膜形态和功能直到 48 周龄时都正常。由于暴露于过高的光水平或磷酸二酯酶 6b 基因突变引起的光感受器损失不受 Tspo 缺乏的影响。光损伤后视网膜单核吞噬细胞的反应状态在 Tspo-KO 和对照小鼠中相似。我们的数据表明，缺乏内源性 TSPO 不会直接影响这两种视网膜变性模型中光感受器变性或小胶质细胞激活的程度。因此，我们假设 TSPO 与其配体的相互作用可能需要调节疾病的进展。
