Table 1.
Mediators in diabetic retinopathy, including cytokines, chemokines, growth factors, adhesion molecules, neurotoxins and others. These mediators are either upregulated (up arrow) or downregulated (down arrow) in diabetic retinopathy.
| Mediators | Regulation | Relevance | References |
|---|---|---|---|
| Cytokines | |||
| IL-1β | ↑ | Immuno-stimulation Increased ICAM-1 | [28,168,169,170,171] |
| IL-6 | ↑ | Immuno-stimulation | [172,173] |
| IL-8 | ↑ | Immuno-stimulation | [173] |
| IL-18 | ↑ | Immuno-stimulation | [174,175,176] |
| VEGF | ↑ | Immuno-stimulation Angio-stimulation Neuroprotective | [177] |
| TNFα | ↑ | Immuno-stimulation Increased ICAM-1 Increased leukostasis | [28,168,178,179,180] |
| COX-2 | ↑ | Immuno-stimulation | [180] |
| Chemokines | |||
| CCL-2 | ↑ | Immuno-stimulation | [181] |
| CCL-4 | ↑ | Immuno-stimulation | [181] |
| CXCL-9 | ↑ | Immuno-stimulation | [181] |
| CXCL-10 | ↑ | Immuno-stimulation | [181] |
| MCP-1 | ↑ | Immuno-stimulation Increased fibrosis Angio-stimulation | [28,173,182] |
| CX3CL1 | ↑ | Immuno-stimulation Neuroprotective | [183] |
| Growth factors | |||
| NGF | ↓ | Cellular toxicity | [184] |
| PEDF | ↓ | Cellular toxicity | [184] |
| IRBP | ↓ | Cellular toxicity | [184] |
| Somatostatin | ↓ | Cellular toxicity | [184] |
| Adhesion molecules | |||
| ICAM-1 | ↑ | Increased leukostasis | [64,65,66] |
| VCAM-1 | ↑ | Increased leukostasis | [64,65,66] |
| Neurotoxins | |||
| ROS | ↑ | Cellular toxicity | [185] |
| NO | ↑ | Cellular toxicity | [185] |
| Glutamate | ↑ | Cellular toxicity | [185] |
| Caspase-3 | ↑ | Cellular toxicity | [185] |
| Others | |||
| LPS | ↑ | Immuno-stimulation Cellular toxicity | [106] |
| AGE | ↑ | Immuno-stimulation Cellular toxicity | [49,50,51,52,53,54,55,56] |
| LEP | ↑ | Immuno-stimulation Cellular toxicity | [49,50,51,52,53,54,55,56] |
| Angiopoietin-2 | ↑ | Angio-stimulation | [186,187] |
| RBP4 | ↑ | Immuno-stimulation Neurotoxic Increased vascular leakage | [174,175,176] |
| NOX-1/4 | ↑ | Immuno-stimulation Increased leukostasis Increased ROS Increased vascular leakage | [188] |
| MMP-2/9 | ↑ | Immuno-stimulation Increased chemokines Neurotoxic | [189,190,191,192,193,194] |
| STAT3 | ↑ | Immuno-stimulation Increased vascular leakage | [195,196] |
| Wnt | ↑ | Immuno-stimulation Increased ROS | [197] |
IL: interleukin; VEGF: vascular endothelial growth factor; TNF: tumor necrosis factor; COX: cyclooxygenase; CCL: chemokine (C-C motif) ligand; CXCL: chemokine (C-X-C motif) ligand; MCP: monocyte chemoattractant protein-1; CX3CL: chemokine (C-X3-C motif) ligand; NGF: nerve growth factor; PEDF: pigment epithelium-derived factor; IRBP: iron-responsive element-binding protein; ICAM: intercellular adhesion molecule; VCAM: vascular cell adhesion protein; ROS: reactive oxygen species; NO: nitric oxide; LPS: lipopolysaccharide; AGE: advanced glycation end products; LEP: leptin; RBP: retinol binding protein; NOX: nicotinamide adenine dinucleotide phosphate (NADPH) oxidase; MMP: matrix metalloproteinase; STAT: signal transducer and activator of transcription; Wnt: wingless.