Investigation of the role of CD1d-restricted invariant NKT cells in experimental choroidal neovascularization

• Published in: Biochemical and biophysical research communications Vol. 374; no. 1; pp. 38 - 43
• Main Authors: Hijioka, Kuniaki, Sonoda, Koh-Hei, Tsutsumi-Miyahara, Chikako, Fujimoto, Takeshi, Oshima, Yuji, Taniguchi, Masaru, Ishibashi, Tatsuro
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 12.09.2008
• Subjects: Age-related macular degeneration; Animals; Antibodies - immunology; Antigens, CD1 - genetics; Antigens, CD1 - physiology; Antigens, CD1d; Chemokine CXCL16; Chemokine CXCL6 - genetics; Choroidal neovascularization; Choroidal Neovascularization - chemically induced; Choroidal Neovascularization - genetics; Choroidal Neovascularization - immunology; Coculture Techniques; Disease Models, Animal; Epithelial Cells - cytology; Female; Galactosylceramides - toxicity; Genes, T-Cell Receptor alpha; Innate immunity; Interleukin-6 - genetics; Interleukin-6 - metabolism; Killer Cells, Natural - immunology; Mice; Mice, Inbred C57BL; Mice, Knockout; Natural killer T cell; Pigment Epithelium of Eye - cytology; Spleen - cytology; T-Lymphocytes - immunology; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - genetics; Vascular Endothelial Growth Factor A - metabolism; Innate immunity; Natural killer T cell; Choroidal neovascularization; Age-related macular degeneration; Vascular endothelial growth factor
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2008.06.080

Choroidal neovascularization (CNV) is directly related to visual loss in age-related macular degeneration and other macular disorders. We have investigated the role of CD1d-restricted invariant natural killer T (NKT) cells in laser-induced experimental CNV. Quantitative real-time PCR detected increased expression of NKT cell-related genes (Vα14 and CXCL16) in whole eyes undergoing CNV, indicating local accumulation of NKT cells. We found a significant reduction of CNV and lower concentrations of vascular endothelial growth factor (VEGF) in ocular fluid in two different NKT cell-deficient mice, CD1d knockout (KO) and Jα18 KO mice. We also established in vitro co-cultures of retinal pigment epithelial cells and splenic NKT cells, and confirmed NKT cells could produce VEGF in the dish. Moreover, inoculating α-galactosylceramide, the ligand for NKT cells, into the vitreous cavity of C57BL/6 mice promoted CNV. We concluded that NKT cells play an important role in CNV as an inducer of VEGF.