Angiogenic and Antiangiogenic Factors in Proliferative Diabetic Retinopathy

Authors: Simo, Rafael; Carrasco, Esther; Garcia-Ramirez, Marta; Hernandez, Cristina

Source: Current Diabetes Reviews, Volume 2, Number 1, February 2006 , pp. 71-98(28)

Publisher: Bentham Science Publishers

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Abstract:

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-β ), thrombospondin (TSP) and somatostatin are also among the intraocullary synthesized antiangiogenic factors.

Keywords: Diabetic retinopathy; Angiogenic factors; Antiangiogenic factors; Vitreous fluid; Angiopoietin; Angiostatin; basic fibroblast growth factor; Connective tissue growth factor; Endostatin; insulin-like growth factor

Document Type: Research article

Affiliations: 1: Diabetes Research Unit, Endocrinology Division, Hospital Universitari Vall d'Hebron, Pg. Vall d'Hebron 119-129, 08035 Barcelona, Spain.

Publication date: 2006-02-01

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Current Diabetes Reviews publishes frontier reviews on all the latest advances on diabetes and its related areas e.g. pharmacology, pathogenesis, complications, epidemiology, clinical care, and therapy.

The journal's aim is to publish the highest quality review articles dedicated to clinical research in the field. The journal is essential reading for all researchers and clinicians who are involved in the field of diabetes.

Angiogenic and Antiangiogenic Factors in Proliferative Diabetic Retinopathy

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