*4.4.4.1 Monocyte chemoattractant protein-1 (MCP-1/CCL2)*

Monocyte chemoattractant protein-1 (MCP-1/CCL2) is considered one of the key chemokines that regulate migration and infiltration of monocytes/macrophages [115]. The expression of MCP-1 is regulated by NF-κB and MCP-1 can induce VEGF production [116]. Both CCL2 and its receptor CCR2 have been demonstrated to be induced and involved in various diseases [115]. Diabetic patients have shown elevated levels of MCP-1 in vitreous and its levels are higher in the vitreous than in the serum indicating local production of MCP-1 [117]. Studies have shown that there is a significant association between the vitreous MCP-1 levels and DR severity [118]. The MCP-1 is also a potent chemotactic factor for monocytes and macrophages that can stimulate them to produce superoxide and other mediators. Following hyperglycemia, retinal pigment epithelial (RPE) cells, endothelial cells, and Müller's glial cells are of utmost importance for MCP-1 production, and vitreous MCP-1 levels rise in patients with DR. Increased expression of the MCP-1 in the eyes can also play a significant role in the pathogenesis of DR [119]. Interferon-gamma inducible protein 10 (IP-10) is a CXC chemokine that is expressed at higher levels in the vitreous of diabetic patients [120], and its vitreous levels are higher than its serum levels [121]. Anti-inflammatory cytokines such as IL-10 and IL-13 may be involved more in the pathogenesis of DR and CRVO than in other diseases and both cytokines and chemokines may be correlated to VEGF in the vitreous fluid and the inflammatory reaction may be more active in CRVO than in DR [122].
