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Review: The renin-angiotensin-aldosterone system and the eye in diabetes

International Centre for Circulatory Health & Department of Epidemiology and Public Health, Faculty of Medicine, Imperial College at St Mary's, Norfolk Place, London, W2 1PG, UK, d.strain@ ic.ac.uk

Nish Chaturvedi

International Centre for Circulatory Health & Department of Epidemiology and Public Health, Faculty of Medicine, Imperial College at St Mary's, Norfolk Place, London, W2 1PG, UK

Diabetic retinopathy is the leading cause of blindness in the under 65s, and with the burden of disease case load expected to exceed 200 million worldwide within 10 years, much effort is being spent on prophylactic interventions. Early work focused on improving glycaemic control; however, with the publication of EURODIAB Controlled trial of Lisinopril in Insulin-dependent Diabetes (EUCLID) and United Kingdom Prospective Diabetes Study (UKPDS), the focus has recently moved to control of blood pressure and specifically the renin-angiotensin system (RAS). There is a large body of evidence for a local RAS within the eye that is activated in diabetes. This appears to be directly responsible, as well as indirectly through other mediators, for an increase in concentration of vascular endothelial growth factor (VEGF), a selective angiogenic and vasopermeability factor that is implicated in the pathogenesis of diabetic retinopathy. Inhibition of angiotensin-converting enzyme appears to reduce concentrations of VEGF, with a concurrent anti-proliferative effect independent of systemic VEGF levels or blood pressure. Angiotensin II (Ang II) Type 1 (AT₁) receptor blockade has been shown to reduce neovascularisation independent of VEGF levels in animal models. This may be due to antagonism of activation of mitogen-activated protein kinase, which is a potent cellular proliferation stimulator, by Ang II, although this needs further evaluation.

Key Words: local renin-angiotensin system • diabetic retinopathy • vascular endothelial growth factor

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Journal of Renin-Angiotensin-Aldosterone System, Vol. 3, No. 4, 243-246 (2002)
DOI: 10.3317/jraas.2002.045


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