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Updated: Sep 25, 2026
Targeted Knockdown of Genes in the Choroid Plexus
Published on: June 16, 2023
Targeted disruption of the CD18 or ICAM-1 gene inhibits choroidal neovascularization
Eiji Sakurai1, Hogara Taguchi, Akshay Anand
1Department of Ophthalmology, University of Kentucky, Lexington, Kentucky 40536-0284, USA.
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.
Insights
Leukocyte adhesion molecules CD18 and ICAM-1 play a key role in choroidal neovascularization (CNV). Mice lacking CD18 or ICAM-1 showed significantly reduced CNV development and leakage, indicating their importance.
Area of Science:
- Ophthalmology
- Immunology
- Vascular Biology
Background:
- Choroidal neovascularization (CNV) is a major cause of vision loss.
- Leukocyte adhesion molecules are crucial for immune cell trafficking and inflammation.
- The specific roles of CD18 and ICAM-1 in CNV pathogenesis are not fully understood.
Purpose of the Study:
- To investigate the involvement of leukocyte adhesion molecules CD18 and intercellular adhesion molecule (ICAM)-1 in the development of laser-induced choroidal neovascularization (CNV).
Main Methods:
- Laser photocoagulation was used to induce CNV in wild-type, CD18-deficient, and ICAM-1-deficient mice.
- Expression of CD18 and ICAM-1 was assessed by immunostaining post-injury.
- CNV volume and fluorescein leakage were quantified using confocal microscopy and angiography.
Main Results:
- Upregulation of ICAM-1 and CD18-positive leukocyte infiltration occurred rapidly after laser injury.
- CD18- and ICAM-1-deficient mice exhibited significantly reduced CNV leakage and lesion volume compared to wild-type controls.
- Fewer lesions showed significant fluorescein leakage in CD18- and ICAM-1-deficient mice.
Conclusions:
- Leukocyte adhesion to vascular endothelium, mediated by CD18 and ICAM-1, plays a critical and nonredundant role in the development of laser-induced CNV.
- Targeting these adhesion molecules may offer a therapeutic strategy for CNV.
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