Deletion of TSPO causes dysregulation of cholesterol metabolism in mouse retina

Fahad Farhan, Mohammad Almarhoun, Aileen Wong, Amy S. Findlay, Chris Bartholomew, Mark T.S. Williams, Toby W. Hurd, Xinhua Shu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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.
Original languageEnglish
Article number3066
Number of pages16
JournalCells
Volume10
Issue number11
DOIs
Publication statusPublished - 7 Nov 2021

Keywords

  • TSPO; retina; cholesterol; inflammation; age-related macular degeneration

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