Cytokines and the Pathogenesis of Macular Edema in Branch Retinal Vein Occlusion

Figure 3

Pathogenesis of macular edema (hypothesis). BRVO not only causes retinal hypoxia but also produces inflammation secondary to retinal hemorrhage. As a result, expression of VEGF and inflammatory cytokines increases, resulting in disruption of the BRB with the development and progression of macular edema. Activation of VEGFR-1 by both VEGF and PlGF plays a role in recruitment of leukocytes and also upregulates expression of inflammatory cytokines. In addition, activation of VEGFR-2 by VEGF increases vascular permeability and enhances the expression of inflammatory cytokines such as MCP-1 and ICAM-1 via NF-κB, leading to chemotaxis and adhesion of leukocytes to the vascular endothelium along with a decrease of blood flow velocity. Reduction of blood flow velocity creates a positive feedback loop, which further exacerbates retinal hypoxia. Increased leukocyte chemotaxis and adhesion also enhances inflammation, creating another positive feedback loop. According to this hypothesis, the pathological mechanism becomes more complicated and the influence of inflammation increases as BRVO becomes chronic.