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

Biochem Biophys Res Commun. 2008 Sep 12;374(1):38-43. doi: 10.1016/j.bbrc.2008.06.080. Epub 2008 Jul 9.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / immunology
  • Antigens, CD1 / genetics
  • Antigens, CD1 / physiology*
  • Antigens, CD1d
  • Chemokine CXCL16
  • Chemokine CXCL6 / genetics
  • 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
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Killer Cells, Natural / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Pigment Epithelium of Eye / cytology
  • Spleen / cytology
  • T-Lymphocytes / immunology*
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism


  • Antibodies
  • Antigens, CD1
  • Antigens, CD1d
  • Chemokine CXCL16
  • Chemokine CXCL6
  • Cxcl16 protein, mouse
  • Galactosylceramides
  • Interleukin-6
  • Vascular Endothelial Growth Factor A
  • alpha-galactosylceramide