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Jiyang Cai, Yan Chen; Protective Roles of Choroidal γδ T Cells in Chronic Models of RPE Degeneration. Invest. Ophthalmol. Vis. Sci. 2019;60(9):1245.
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© ARVO (1962-2015); The Authors (2016-present)
Mechanisms of cell-mediated immunity during degeneration of the retinal pigment epithelium (RPE) remain largely unclear. We previously reported that choroidal gamma delta T cells (GDTs) protect against sodium iodate-induced injury to the RPE. The main goal of the current study is to define the functions of GDTs in a chronic model of RPE degeneration
Wild type or T cell receptor delta chain knockout mice were fed with a high fat, cholesterol-rich diet. The treatment was started when animals reached 12 months of age and lasted for 6 weeks. After additional 6 weeks of recovery on control diet, retinal and RPE pathologies were assessed by fundus photography, histopathology and immunostaining of RPE flat mount. Cytokine-mediated cell-cell interactions among GDTs, RPE and retinal microglia were examined in ex vivo tissue culture
Middle-aged wild type mice on high fat diet developed a moderate and transient inflammatory response in the retina. Mice with deficiency in GDTs showed increased sensitivity to high fat diet-induced RPE injury that was not recovered after switching back to control diet. Interleukin 17 (IL-17), produced by choroidal GDTs, activated IL-6 production from the RPE. IL-6 potentiated microglial phagocytosis and degradation of photoreceptor outer segments
The cytokine mediated signaling cascade from choroidal GDTs to RPE to retinal microglia has regulatory and protective roles during inflammation resolution in response to chronic stress conditions in the outer retina
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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