Cytokine Profiles and the Effect of Intravitreal Aflibercept Treatment on Experimental Choroidal Neovascularization

The purpose of our study was to investigate the profiles of inflammatory cytokines and the macrophage polarization gene in a choroidal neovascularization (CNV) mouse model before and after intravitreal aflibercept treatment.

The CNV mouse model was conducted by laser photocoagulation. A total of 58 cytokines were measured by the multiplex mouse cytokine antibody array. The macrophage polarization genes were tested by reverse transcription polymerase chain reaction. The relationship between the cytokines and the CNV lesion area was analyzed by correlation.

MIP-1a on day 3 after laser photocoagulation, MCP-5 and Fas-L on day 7, and IL-15 and IL-7 on day 14 were significantly upregulated (p < 0.001, fold change >10.0). After the intravitreal aflibercept treatment, GM-CSF and MCP-1 on day 3 and TIMP-1 on days 7 and 14 were the most significantly upregulated cytokines (p < 0.001, fold change >10.0). MIP-1 on day 3, IL-13 and Fas-L on day 7, and Fas-L on day 14 were the most significantly downregulated cytokines after intravitreal aflibercept treatment (p < 0.001, fold change >5.0). M2 polarization and VEGFA genes were significantly increased in the CNV formation, whereas aflibercept suppressed M2 polarization and VEGFA genes. IL-7 was negatively related to the CNV lesion area on day 14 after intravitreal aflibercept treatment (r = -0.938, p = 0.006).

The inflammatory cytokines and the M1/M2 macrophage genes significantly changed in the CNV mouse model. This result suggests that inflammatory cytokines and macrophages play a critical role in the physiopathology of CNV.