Figure 1.

Inflammation during diabetic retinopathy. Increased plasma levels of blood glucose, vascular endothelial growth factor (VEGF), advanced glycation end-products (AGE), reactive oxygen species (ROS), chemokine (C-C motif) ligand 2 (CCL2), interleukins 1 beta and 8 (IL-1β and IL-8), and tumor necrosis factor alpha (TNF-α) profuse through leaky capillary endothelial cell junctions by the actions of VEGF. IL-1β, AGE, ROS, and TNF-α activate microglia to produce glutamate, matrix metalloproteinases (MMPs), nitric oxide synthases (NOS), IL-1β, and TNF-α. IL-1β and TNF-α drive the production of caspase 3, which along with glutamate is neurotoxic to retinal ganglion cells. Caspases also damage capillary endothelial cells and pericytes. TNF-α leads to production of ICAM-1 and VCAM that help recruit macrophages through the capillary walls sustaining a chronic inflammatory response. COX-2 is also a product stimulated by IL-1β and TNF-α.