Journal
CURRENT DIABETES REVIEWS
Volume 2, Issue 1, Pages 71-98Publisher
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/157339906775473671
Keywords
Diabetic retinopathy; Angiogenic factors; Antiangiogenic factors; Vitreous fluid; Angiopoietin; Angiostatin; basic fibroblast growth factor; Connective tissue growth factor; Endostatin; insulin-like growth factor; Hepatocyte growth factor; Pigment epithelium-derived factor; Platelet-derived growth factor; Somatostatin; Stromal cell-derived factor-1; Transforming growth factor; Thrombospondin; Vascular endothelial growth factor
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Funding
- Novo Nordisk Pharma S.A.
- Novartis Pharma S.A.
- Ministerio de Ciencia y Tecnologia [SAF2003-00550]
- Instituto de Salud Carlos III [G03/212, C03/08]
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Diabetic retinopathy continues to be the leading cause of legal blindness among working-age individuals. The earliest histological features of diabetic retinopathy include neuroretinal damage, capillary basement membrane thickening, loss of pericytes and loss of endothelial cells. At advanced stages, neovascularization, the hallmark of proliferative diabetic retinopathy (PDR) occurs, and blindness can result from relentless abnormal fibrovascular proliferation with subsequent bleeding and retinal detachment. Macular oedema is another retinal complication of diabetes that is responsible for a major part of vision loss, particularly in type 2 diabetes. The breakdown of the blood retinal barrier and the consequent vascular leakage and thickening of retina are the main events involved in its pathogenesis. Although a tight control of both blood glucose levels and hypertension are essential to prevent or arrest progression of the disease, the recommended goals are difficult to achieve in many patients. Laser photocoagulation treatment soon after the onset of PDR significantly reduces the incidence of severe vision loss. However, the optimal timing for laser treatment is frequently passed and, in addition, it is not uniformly successful in halting visual decline. For all these reasons, new pharmacological treatments based on the understanding of the pathophysiological mechanisms of diabetic retinopathy have been developed in recent years. There is mounting evidence to suggest that angiogenic factors play a crucial role in PDR development, vascular endothelial growth factor (VEGF) being the most relevant. Other growth factors or cytokines such as insulin-like growth factor I (IGF-1), hepatocyte growth factor (HGF), basic fibroblast growth factor (b-FGF), platelet derived growth factor (PDGF), pro-inflammatory cytokines and angiopoetins, are also involved in the pathogenesis of PDR. However, the intraocular synthesis of angiogenic factors is counterbalanced by the synthesis of antiangiogenic factors. Therefore, the balance between the angiogenic and antiangiogenic factors rather than angiogenic factors themselves will be crucial in determining the progression of PDR. The main antiangiogenic factor is the pigment epithelium derived factor (PEDF) but the transforming growth factor beta (TGF-beta), thrombospondin (TSP) and somatostatin are also among the intraocullary synthesized antiangiogenic factors.
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