Abstract
Purpose: :
CD40, a transmembrane-glycoprotein member of the tumor necrosis factor (TNF) receptor gene family, is expressed on numerous cell types including most professional antigen-presenting cells such as monocytes, and endothelial cells. It has been reported that signals via CD40-CD40L ligation induce the expression of vascular endothelial growth factor (VEGF) by endothelial cells and monocytes, which promotes vascularization. In this study, we investigated whether CD40 could play an important role in experimentally induced choroidal neovascularization (CNV).
Methods: :
C57BL/6J mice with laser-induced rupture of Bruch's membrane were given intraperitoneal injection of anti-CD40 stimulating antibody or vehicle. After 7 days, they were perfused with fluorescein-labeled dextran, and the area of CNV was measured on choroidal flatmounts by image analysis. In addtion, CD40 mRNA expression in the retina was measured by real-time PCR 7 days after laser photocoagulation.
Results: :
CD40 mRNA was increased in the retina 7 days after laser photocoagulation (p=0.0433). Intraperitoneal injection of 300 µg/day anti-CD40 stimulating antibody on 1, 3, and 5 days after rupture of Bruch's membrane resulted in a approximately 30% enlargement in the area of CNV compared with those injected with vehicle (p=0.0119).
Conclusions: :
We observed increased CD40 expression in the retina induced CNV by laser photocoagulation, and stimulation of CD40 resulted in a significant increase in the size of CNV. These data suggested that CD40 might be a promoting factor on vascularization in CNV.
Keywords: age-related macular degeneration • choroid: neovascularization • immunomodulation/immunoregulation