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Zhen-Yang Zhao, Pei Xu, Valentina Reffatto, Yuejin Liang, Jiaren Sun, Yan Chen, Deming Sun, Jiyang Cai; Protective Roles of γδT-Cells in Model of RPE Injury. Invest. Ophthalmol. Vis. Sci. 2016;57(12):477. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Chronic inflammation and immune responses are key factors determining the progression of age-related macular degeneration. We recently reported activation of choroidal γδT-cells and their production of interleukin-17 in Nrf2-deficient mice fed with high-fat diet, a model of age-related degeneration of the retinal pigment epithelium (RPE). The purpose of the current study is to further characterize the functions of γδT-cells after RPE injury.
Wild-type (WT) C57 BL/6J and TCRδ-/- mice were treated with 15 mg/kg body weight of sodium iodate via tail vein injection. RPE and retinal pathology was monitored for up to 7 days by fundus photography, optical coherence tomography (OCT) and optokinetic tracking (OKT), and further validated by histopathology grading. Infiltration of γδT-cells was examined through tissue immunostaining and flow cytometry. Purified γδT-cells from retina and choroidal were assessed by quantitative RT-PCR for their marker gene expression. Adoptive transfer of WT γδT-cells was performed to rescue the phenotype in TCRδ-/- mice.
Low dose sodium iodate caused minimal retinal pathology in WT mice, but markedly induced RPE atrophy, retinal thinning and visual function decline in TCRδ-/- mice. Immunostaining of choroidal flat mount identified increased γδT-cell infiltration, which was further confirmed by flow cytometry. Purified choroidal γδT-cells expressed immunosuppressive genes, such as IL-10 and IL-4, but not interferon-γ. Transplant of WT γδT-cells to TCRδ-/- mice restored its tolerance to sodium iodate challenge. Ex vivo co-culture of γδT-cells with RPE explants activated IL-10 production.
The regulatory γδT-cells in the choroid can maintain immune homeostasis in the back of the eye, and are protective against RPE injury.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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