The role of growth factors in the pathogenesis of diabetic retinopathy.
Diabetic retinopathy (DR) is the most severe of several ocular complications of diabetes. The earliest clinical signs of DR are microaneurysms and haemorrhages. Later signs include dilated, tortuous irregular veins and retinal non-profusion, leading to retinal ischaemia that ultimately results in neovascularisation. Diabetic macular oedema, which involves the breakdown of the blood-retinal barrier, also occurs and is responsible for a major part of vision loss, particularly in Type 2 diabetes. The pathogenesis of DR is very complex. Many biochemical mechanisms have been proposed as explanations for the development and progression of DR. Chronic hyperglycaemia leads to oxidative injury, microthrombi formation, cell adhesion molecule activation, leukostasis and cytokine activation. Next, ischaemia-mediated overexpression of growth factors and cytokines occurs. These factors include vascular endothelial growth factor, insulin-like growth factor-1, angiopoetin-1 and -2, stromal-derived factor-1, fibroblast growth factor-2 and tumour necrosis factor. Because of the complex interplay between these factors, targeting a single growth factor will be unlikely to result in therapeutic inhibition of angiogenesis. These growth factors no doubt act in synergy to mediate the steps of angiogenesis, including protease production, endothelial cell proliferation, migration and tube formation. This review attempts to provide an overview of perspectives regarding the pathogenesis of this disease. The focus, however, is on describing the unique features of selected relevant factors and how each growth factor may act in a synergistic manner with other factors.
Grant
Maria B
MB
University of Florida, Department of Pharmacology and Therapeutics, 1600 SW Archer Road, PO Box 100267, Gainesville, FL 32610, USA. grantma@pharmacology.ufl.edu
Afzal
Aqeela
A
Spoerri
Polyxenie
P
Pan
Hao
H
Shaw
Lynn C
LC
Mames
Robert N
RN
D000818:Animals; D003930:Diabetic Retinopathy / Q000503:physiopathology*; D016228:Endothelial Growth Factors / Q000502:physiology; D016222:Fibroblast Growth Factor 2 / Q000502:physiology; D006133:Growth Substances / Q000502:physiology*; D006801:Humans; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology
D016228:Endothelial Growth Factors; D006133:Growth Substances; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2