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K.-H. Sonoda, K. Hijioka, C. Tsutsumi-Miyahara, T. Ishibashi; Investigation of the Role of Cd1d-restrected Invariant Nkt Cells During the Formation of Experimental Choroidal Neovascularization. Invest. Ophthalmol. Vis. Sci. 2008;49(13):205. doi: https://doi.org/.
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Choroidal neovascularization (CNV) is directly related to visual loss in age-related macular degeneration and other macular disorders. Several studies suggested the involving local inflammation to form CNV. Natural Killer T (NKT) cells belong to a specialized population of lymphocytes that coexpress the T cell receptor and NK marker. In this study, we elucidated the role of NKT cells, which restricted CD1d molecule and participate in the innate immune response, in laser-induced experimental CNV
We used Female 8-10 weeks C57BL/6 mice, and two independent NKT cell-deficient mice; CD1d knockout (KO) mice and Ja18 KO mice. Experimental CNV was induced with rupturing in Bruch's membrane by laser photocoagulation (PC). Seven days after PC, the eyes were enucleated and the areas of CNV were measured in the choroidal flat mounts.
We detected the increase of NKT cell-related genes (Va14 and CXCL16) in the whole CNV-induced eye by quantitative real-time PCR, which indicated local accumulation of NKT cells. Both CD1d KO mice and Ja18 KO mice showed significant reduction of experimental CNV and decrease of VEGF in the concentration of ocular fluid at 24h after PC. In vitro co-culture of CD1d-positive retinal pigment epithelial cells and purified splenic T cells, which partially resembled the interaction of resident ocular cells and NKT cells, showed the decrease of VEGF in the cultured supernatant in either NKT cell-deficiency or inhibiting NKT cell activation by the treatment of anti-CD1d antibody.
NKT cells play an important role to form CNV as one of the inducer of VEGF.
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