Targeted disruption of the CD18 or ICAM-1 gene inhibits choroidal neovascularization

Invest Ophthalmol Vis Sci. 2003 Jun;44(6):2743-9. doi: 10.1167/iovs.02-1246.


Purpose: To investigate the role of the leukocyte adhesion molecules CD18 and intercellular adhesion molecule (ICAM)-1 in the development of choroidal neovascularization (CNV).

Methods: Laser photocoagulation was used to induce CNV in wild-type C57BL/6J mice and species-specific counterparts with targeted homozygous disruption of the CD18 or ICAM-1 gene. Expression of CD18 and ICAM-1 after laser injury was assessed by immunostaining. CNV responses were compared on the basis of en masse volumetric measurements obtained by confocal microscopy 2 weeks after laser injury and by determination of fluorescein angiographic leakage at 1, 2, and 4 weeks after laser injury.

Results: The site of laser injury showed upregulation of ICAM-1 and invasion by CD18-positive leukocytes within 1 day of laser injury. Significantly fewer lesions exhibited fluorescein leakage defined to be pathologically significant in CD18-deficient mice at weeks 1, 2, and 4 weeks and in ICAM-1-deficient mice at 1 and 4 weeks, compared with the control. There were a significantly greater number of lesions without fluorescein leakage in CD18-deficient mice than in the other two groups at all time points. The volume of CNV in CD18- and ICAM-1-deficient mice was significantly less than in wild type.

Conclusions: These data suggest a nonredundant role for leukocyte adhesion to vascular endothelium in the development of laser-induced choroidal neovascularization.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • CD18 Antigens / genetics
  • CD18 Antigens / physiology*
  • Capillary Permeability
  • Choroidal Neovascularization / pathology
  • Choroidal Neovascularization / prevention & control*
  • Fluorescein
  • Fluorescein Angiography
  • Gene Deletion*
  • Gene Targeting
  • Intercellular Adhesion Molecule-1 / genetics
  • Intercellular Adhesion Molecule-1 / physiology*
  • Laser Coagulation
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microscopy, Confocal
  • Up-Regulation


  • CD18 Antigens
  • Intercellular Adhesion Molecule-1
  • Fluorescein