The role of CD40 and CD40L in the pathogenesis of an experimental model of choroidal neovascularization

Objective: To evaluate the effect of intravitreal injection with anti-CD40 ligand antibody (anti-CD40L) on choroidal neovascularization (CNV) in a laser-induced CNV mouse model. Methods: Anti-CD40L (0.5 mg/ml, 1 μl), anti-VEGF (0.5 mg/ml, 1 μl) or PBS (1×, 1 μl) was injected into the vitreous body of C57BL/6J mice at day 3 after laser photocoagulation. Changes in CNV lesions were evaluated by immunofluorescence staining and immunohistochemistry of the CNV sites in retinal pigment epithelium (RPE)-choroid-sclera flat mounts. Expression of VEGF was detected by real-time quantitative PCR (RT-PCR) to explore the inhibitory effect of anti-CD40L on CNV progression. Results: Compared with the CNV model group, anti-CD40L group and anti-VEGF group showed significant regression of the experimental CNV as represented by a 42.87% and 50.87% reduction of the hyper-fluorescence area of the CNV lesion, respectively (both P<0.01). Histological images shows that the CNV lesions in anti-CD40L group were smaller in diameter and had thinner centers compared with those in the control group. Immunohistochemistry showed that the expression level of VEGF-A was suppressed after up-regulation of CD40L. Real Time-PCR analysis showed that the expression of VEGF in the photocoagulated choroid tissue was reduced after blocking CD40L. Conclusion: Anti-CD40L effectively inhibited CNV in the experimental laser-induced CNV model, suggesting that antiCD40L may prove to be a clue for the treatment of CNV.