Main pathogenetic events in diabetic retinopathy

Schematic representation of the main pathogenetic events in the development and progression of diabetic retinopathy (DR) depicted from healthy (left) to advanced-stage DR (right). Non-proliferative DR is characterized by vascular changes such as thickening of the basement membrane, endothelial injury that leads to the disruption of the tight junctions and pericyte loss, resulting in dot haemorrhages, microaneurysms and hard exudates. Vascular endothelial growth factor (VEGF) and pro-inflammatory cytokine production (IL-1β, tumour necrosis factor, IL-6, IL-8 and monocyte chemoattractant protein 1) by the retinal pigment epithelium (RPE), glial cells and macrophages also contribute to the vascular changes. Endothelial damage leads to vasoconstriction owing to vasoconstrictor release (endothelin 1 and thromboxane A2) and hypoxia in pre-proliferative DR, which is aggravated owing to the capillary occlusion. The severe hypoxia in end-stage DR leads to neovascularization. These new blood vessels tend to grow into the vitreous body and are prone to rupture.