*4.4.3.1 Interleukin-6 (IL-6)*

IL-6 is a cytokine regulates the expression of matrix metalloproteinases (MMPs) which is a primary constituent of the vitreous [86, 87] and it also regulates immune response, increases permeability of vessels and initiates angiogenesis [88, 89]. Studies, have indicated that IL-8, VEGF-A, and PlGF demonstrated a strong correlation in vitreous and aqueous of patients with PDR. The aqueous may serve as a proxy for vitreous for some cytokines involved in PDR. More recently anti-VEGF injections have been able to decrease VEGF-A levels in aqueous, however they did not significantly affect other cytokines, indicating a need for other targeted therapies in PDR management [90]. Role of IL-6 in neovascularization, a key clinical feature of DR, is shown in studies that show IL-6 can not only promote angiogenesis directly but support angiogenesis by inducing expression of VEGF, an angiogenic factor [91]. Hence, the role of IL-6 and IL-8 as angiogenic and factor for causing neovascularization is supported.
