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Minhua Wang, Lian Zhao, Wenxin Ma, Robert Fariss, Wai Wong; Role of Translocator Protein (TSPO) in the Regulation of Microglial Function in the Mouse Retina. Invest. Ophthalmol. Vis. Sci. 2013;54(15):5590.
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Translocator protein (TSPO) is a mitochondria protein that is upregulated in glial cells and serves as a biomarker for neurological disease progression and outcome in the brain. We investigate the expression of TSPO in the retina under normal and injury conditions and its physiological significance.
Expression levels of TSPO and its endogenous ligand, diazepam binding inhibitor (DBI), were examined in (1) uninjured developing and adult mouse retinas, and (2) in models of retinal inflammation and injury (intravitreal administration of LPS or NMDA, optic nerve crush, subretinal hemorrhage) using quantitative PCR and immunohistochemistry. The functional effects of TSPO signaling, assessed by TSPO shRNA knockdown and administration of triakontatetraneuropeptide (TTN), a TSPO ligand, were examined using assays measuring reactive oxygen species (ROS) production and inflammatory factor production.
TSPO is expressed in developing microglia in early retinal development but is downregulated to very low levels in adulthood. DBI is expressed constitutively in Muller glia throughout development. In vitro, cultured primary and BV2 microglia increased in TSPO expression following activation with LPS. In vivo, TSPO expression is specifically increased in activated microglia following LPS administration, as well as following optic nerve crush injury, excitotoxic injury using NMDA, and outer retina injury with subretinal hemorrhage. “Knock-down” of TSPO in BV2 microglia augmented LPS-induced ROS production and TNF-α expression, while administration of TTN conversely decreased these LPS-induced responses.
The low level of endogenous TSPO expression and its strong inducibility in retinal microglia in a variety of injury/disease models indicate that TSPO may serve as a useful biomarker for microglial activation in retinal disease. Increased TSPO signaling following activation may serve to limit microglial ROS production and modulate the dynamics of inflammation resolution in the aftermath of injury.
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