Targeted disruption of the CD18 or ICAM-1 gene inhibits choroidal neovascularization.
OBJECTIVE
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.
Sakurai
Eiji
E
Department of Ophthalmology, University of Kentucky, Lexington, Kentucky 40536-0284, USA.
Taguchi
Hogara
H
Anand
Akshay
A
Ambati
Balamurali K
BK
Gragoudas
Evangelos S
ES
Miller
Joan W
JW
Adamis
Anthony P
AP
Ambati
Jayakrishna
J
D000818:Animals; D018821:CD18 Antigens / Q000235:genetics / Q000502:physiology*; D002199:Capillary Permeability; D020256:Choroidal Neovascularization / Q000473:pathology / Q000517:prevention & control*; D019793:Fluorescein; D005451:Fluorescein Angiography; D017353:Gene Deletion; D018390:Gene Targeting; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000502:physiology*; D017075:Laser Coagulation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D015854:Up-Regulation
D018821:CD18 Antigens; D018799:Intercellular Adhesion Molecule-1; D019793:Fluorescein