Monocyte chemoattractant protein-1 (MCP-1/CCL2) in diabetic retinopathy: latest evidence and clinical considerations

Abstract

Diabetic retinopathy (DR) is considered as a diabetes-related complication that can render severe visual impairments and is also a risk factor for acquired blindness in both developed as well as developing countries. Through fibrovascular epiretinal membranes (ERMs), this condition can similarly lead to tractional retinal detachment. Laboratory efforts evaluating the DR pathogenesis can be provided by ocular vitreous fluid and ERMs resulting from vitrectomy. The clinical stages of DR are significantly associated with expression levels of certain chemokines, including monocyte chemotactic protein-1 (MCP-1) in the intraocular fluid. The MCP-1 is also a known potent chemotactic factor for monocytes and macrophages that can stimulate them to produce superoxide and other mediators. Following hyperglycemia, retinal pigmented 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. In this review, current clinical and laboratory progress achieved on the MCP-1 and the DR concerning neovascularization and inflammatory responses in vitreous and/or aqueous humor of DR patients was summarized. It was suggested that further exploration of the MCP-1/CCR2 axis association between clinical stages of DR and expression levels of inflammatory and angiogenic cytokines and chemokines, principally the MCP-1 might lead to potential therapies aiming at neutralizing antibodies and viral vectors.

Keywords: CCL2; DR; MCP-1; PDR; Retinopathy.

Fig. 1

Involvement of RPE cells, Müller cells in the production of MCP-1 in the retinal inflammation, vascular permeability, and neovascularization following hyperglycemia and diabetes in DR patients. In addition, MCP-1 is the main factor in the recruitment of monocytes and macrophages into the retina, and these type of cells are responsible for ROS production and inflammation. ROS: reactive oxygen species; MCP-1: monocyte chemotactic protein-1; RPE cell: retinal pigment epithelium cell