Neurovascular unit in diabetic retinopathy: pathophysiological roles and potential therapeutical targets

Table 1 Pathological features of the neurovascular unit in diabetic retinopathy (DR)

Pathological Changes	Characteristics	References
Neurodegeneration	Loss of retinal ganglion cells and amacrine cells	[36,37,38,39,40]
Neurodegeneration	Decrease of NFL, IPL and INL	[37, 38, 40,41,42]
Reactive gliosis	Activation of astrocytes and Müller cells	[15, 43, 44]
Reactive gliosis	Death of Müller cells	[45]
Microvascular Pathology	Impaired neurovascular coupling	[46, 47]
	Basement membrane thickening	[48,49,50]
	Loss of pericytes	[16, 51, 52]
	Formation of microaneurysms	[53, 54]
	Reduction of tight junctions between endothelial cells and apoptosis of endothelial cells	[52, 55,56,57]
	Breakdown of inner BRB	[55,56,57,58]
Immuno-inflammation	Leukostasis	[59,60,61]
	Activation of microglial cells	[62,63,64]
	Production of inflammatory cytokines (TNFα, IL-1β, IL-6, IL-8, MCP-1, VEGF)	[65,66,67,68,69]
RPE and Choroid Pathology	Damage of transportation of ions and water in RPE cells	[70, 71]
	Decrease of 11-cis retinal produced in RPE cells	[71, 72]
	Upregulation of cytokines secreted by RPE cells (VEGF, PDGF, TNFα, IL-6, IL-8,)	[73]
	Reduction of tight junctions between RPE cells	[34, 74,75,76]
	Breakdown of outer BRB	[34, 74,75,76]
	Choroidal degeneration (decreased choroidal thickness, increased Bruch’s membrane thickness, aneurysms, choroidal neovascularization)	[77,78,79]

NFL= nerve fiber layer; IPL= inner plexiform layer; INL= inner nuclear layer; BRB= blood-retinal barrier; TNFα= tumor necrosis factor alpha; IL-1β= interleukin-1beta; IL-6= interleukin-6; IL-8= interleukin-8; MCP-1= monocyte chemoattractant protein 1; VEGF= vascular endothelial growth factor; RPE= retinal pigment epithelium; PDGF= platelet-derived growth factor

ISSN: 2326-0254