Deletion of TSPO Causes Dysregulation of Cholesterol Metabolism in Mouse Retina

• Published in: Cells (Basel, Switzerland) Vol. 10; no. 11; p. 3066
• Main Authors: Farhan, Fahad, Almarhoun, Mohammad, Wong, Aileen, Findlay, Amy S, Bartholomew, Chris, Williams, Mark T S, Hurd, Toby W, Shu, Xinhua
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 07.11.2021; MDPI
• Subjects: ABCA1 protein; Age; age-related macular degeneration; Aging; Animals; ATP-binding protein; Binding sites; Biological Transport; Cholesterol; Cholesterol - metabolism; Choroid - metabolism; Cytokines; Cytokines - metabolism; Ethanol; Gene Deletion; Gene expression; Gene Expression Regulation; Homeostasis; Homeostasis - genetics; Inflammation; Inflammation - genetics; Inflammation Mediators - metabolism; Ligands; Light microscopy; Lipid Metabolism; Lipids; Macular degeneration; Membrane proteins; Metabolism; Mice; Mice, Knockout; Microglia - metabolism; Microglia - pathology; Mitochondria; Phospholipids; Polymerase chain reaction; Protein transport; Proteins; Receptors, GABA - genetics; Receptors, GABA - metabolism; Retina; Retina - metabolism; Retina - pathology; Retinal Pigment Epithelium - metabolism; Steroids; Triglycerides; TSPO; United Kingdom > UK; TSPO; cholesterol; inflammation; retina; age-related macular degeneration
• DOI: 10.3390/cells10113066
• ISSN: 2073-4409

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 knockout (KO) mice using histological, immunohistochemical, biochemical and molecular biological approaches. We found that 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 KO mice. Expression of cholesterol-associated genes ( , , , and ) was significantly downregulated, and production of pro-inflammatory cytokines was markedly increased in KO retinas. Furthermore, microglial activation was also observed in 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.