Beyond glycemia: The influence of systemic inflammation, lipids, and the gut-retina axis in diabetic retinopathy

Figure 1 The figure illustrates how, in diabetic retinopathy, chronic inflammation bridges metabolic stress to retinal vascular and neuronal injury. Activation of Toll-like receptor/receptor for advanced glycation end products-nuclear factor kappa B signaling triggers cytokine cascades, glial activation, and endothelial dysfunction, ultimately leading to leukostasis, vascular leakage, angiogenesis, and neurodegeneration. PRRs: Pattern recognition receptors; TLRs: Toll-like receptors; RAGE: Receptor for advanced glycation end products; PAMPs: Pathogen-associated molecular patterns; DAMPs: Damage-associated molecular patterns; NF-κB: Nuclear factor kappa B; IL: Interleukin; TNF-α: Tumor necrosis factor-alpha; MCP: Monocyte chemoattractant protein; GFAP: Glial fibrillary acidic protein; ICAM-1: Intercellular adhesion molecule 1; VCAM-1: Vascular cell adhesion molecule 1; DR: Diabetic retinopathy; NPDR: Non-proliferative diabetic retinopathy; PDR: Proliferative diabetic retinopathy; VEGF: Vascular endothelial growth factor; IGF-1: Insulin-like growth factor-1; HGF: Hepatocyte growth factor; Ang-2: Angiopoietin 2; bFGF: Basic fibroblast growth factor; MMPs: Matrix metalloproteinases; PDGF: Platelet-derived growth factor.