Investigation of the role of CD1d-restricted invariant NKT cells in experimental choroidal neovascularization.
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 (Valpha14 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 Jalpha18 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 alpha-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.
Hijioka
Kuniaki
K
Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Sonoda
Koh-Hei
KH
Tsutsumi-Miyahara
Chikako
C
Fujimoto
Takeshi
T
Oshima
Yuji
Y
Taniguchi
Masaru
M
Ishibashi
Tatsuro
T
D000818:Animals; D000906:Antibodies / Q000276:immunology; D018949:Antigens, CD1 / Q000235:genetics / Q000502:physiology*; D055610:Antigens, CD1d; D000075743:Chemokine CXCL16; D054427:Chemokine CXCL6 / Q000235:genetics; D020256:Choroidal Neovascularization / Q000139:chemically induced / Q000235:genetics / Q000276:immunology*; D018920:Coculture Techniques; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000166:cytology; D005260:Female; D005699:Galactosylceramides / Q000633:toxicity; D019673:Genes, T-Cell Receptor alpha; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010857:Pigment Epithelium of Eye / Q000166:cytology; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
D000906:Antibodies; D018949:Antigens, CD1; D055610:Antigens, CD1d; D000075743:Chemokine CXCL16; D054427:Chemokine CXCL6; C498926:Cxcl16 protein, mouse; D005699:Galactosylceramides; D015850:Interleukin-6; D042461:Vascular Endothelial Growth Factor A; C493154:alpha-galactosylceramide