{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T22:28:32Z","timestamp":1791325712951,"version":"4.3.1"},"reference-count":45,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,11,7]],"date-time":"2021-11-07T00:00:00Z","timestamp":1636243200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>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 Tspo knockout (KO) mice using histological, immunohistochemical, biochemical and molecular biological approaches. We found that Tspo 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 Tspo KO mice. Expression of cholesterol-associated genes (Nr1h3, Abca1, Abcg1, Cyp27a1 and Cyp46a1) was significantly downregulated, and production of pro-inflammatory cytokines was markedly increased in Tspo KO retinas. Furthermore, microglial activation was also observed in Tspo 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.<\/jats:p>","DOI":"10.3390\/cells10113066","type":"journal-article","created":{"date-parts":[[2021,11,7]],"date-time":"2021-11-07T20:41:14Z","timestamp":1636317674000},"page":"3066","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Deletion of TSPO Causes Dysregulation of Cholesterol Metabolism in Mouse Retina"],"prefix":"10.3390","volume":"10","author":[{"given":"Fahad","family":"Farhan","sequence":"first","affiliation":[{"name":"Department of Biological and Biomedical Sciences, Glasgow Caledonian University, Glasgow G4 0BA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Almarhoun","sequence":"additional","affiliation":[{"name":"Department of Biological and Biomedical Sciences, Glasgow Caledonian University, Glasgow G4 0BA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3618-1897","authenticated-orcid":false,"given":"Aileen","family":"Wong","sequence":"additional","affiliation":[{"name":"Department of Biological and Biomedical Sciences, Glasgow Caledonian University, Glasgow G4 0BA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy S.","family":"Findlay","sequence":"additional","affiliation":[{"name":"MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh EH4 2XU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1153-8389","authenticated-orcid":false,"given":"Chris","family":"Bartholomew","sequence":"additional","affiliation":[{"name":"Department of Biological and Biomedical Sciences, Glasgow Caledonian University, Glasgow G4 0BA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1114-1418","authenticated-orcid":false,"given":"Mark T. S.","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Biological and Biomedical Sciences, Glasgow Caledonian University, Glasgow G4 0BA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toby W.","family":"Hurd","sequence":"additional","affiliation":[{"name":"MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh EH4 2XU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3760-3019","authenticated-orcid":false,"given":"Xinhua","family":"Shu","sequence":"additional","affiliation":[{"name":"Department of Biological and Biomedical Sciences, Glasgow Caledonian University, Glasgow G4 0BA, UK"},{"name":"School of Basic Medical Sciences, Shaoyang University, Shaoyang 422000, China"},{"name":"Department of Vision Science, Glasgow Caledonian University, Glasgow G4 0BA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.ejpb.2015.04.039","article-title":"The genetics of age-related macular degeneration (AMD)\u2014Novel targets for designing treatment options?","volume":"95","author":"Grassmann","year":"2015","journal-title":"Eur. 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