Deletion of TSPO Causes Dysregulation of Cholesterol Metabolism in Mouse Retina
Cholesterol dysregulation has been implicated in age-related macular degeneration (AMD), the most common cause of visual impairment in the elderly. The 18 KDa translocator protein (TSPO) is a mitochondrial outer membrane protein responsible for transporting cholesterol from the mitochondrial outer m...
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| Autores principales: | , , , , , , , |
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| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
MDPI AG
2021
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/4317af5552b84e9aab650b9822531d40 |
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| Sumario: | Cholesterol dysregulation has been implicated in age-related macular degeneration (AMD), the most common cause of visual impairment in the elderly. The 18 KDa translocator protein (TSPO) is a mitochondrial outer membrane protein responsible for transporting cholesterol from the mitochondrial outer membrane to the inner membrane. TSPO is highly expressed in retinal pigment epithelial (RPE) cells, and TSPO ligands have shown therapeutic potential for the treatment of AMD. Here, we characterized retinal pathology of <i>Tspo</i> knockout (KO) mice using histological, immunohistochemical, biochemical and molecular biological approaches. We found that <i>Tspo</i> KO mice had normal retinal morphology (by light microscopy) but showed elevated levels of cholesterol, triglycerides and phospholipids with perturbed cholesterol efflux in the RPE cells of <i>Tspo</i> KO mice. Expression of cholesterol-associated genes (<i>Nr1h3</i>, <i>Abca1</i>, <i>Abcg1</i>, <i>Cyp27a1</i> and <i>Cyp46a1</i>) was significantly downregulated, and production of pro-inflammatory cytokines was markedly increased in <i>Tspo</i> KO retinas. Furthermore, microglial activation was also observed in <i>Tspo</i> KO mouse retinas. These findings provide new insights into the function of TSPO in the retina and may aid in the design of new therapeutic strategies for the treatment of AMD. |
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