Angiotensin and diabetic retinopathy.
Diabetic retinopathy develops in patients with both type 1 and type 2 diabetes and is the major cause of vision loss and blindness in the working population. In diabetes, damage to the retina occurs in the vasculature, neurons and glia resulting in pathological angiogenesis, vascular leakage and a loss in retinal function. The renin-angiotensin system is a causative factor in diabetic microvascular complications inducing a variety of tissue responses including vasoconstriction, inflammation, oxidative stress, cell hypertrophy and proliferation, angiogenesis and fibrosis. All components of the renin-angiotensin system including the angiotensin type 1 and angiotensin type 2 receptors have been identified in the retina of humans and rodents. There is evidence from both clinical and experimental models of diabetic retinopathy and hypoxic-induced retinal angiogenesis that the renin-angiotensin system is up-regulated. In these situations, retinal dysfunction has been linked to angiotensin-mediated induction of growth factors including vascular endothelial growth factor, platelet-derived growth factor and connective tissue growth factor. Evidence to date indicates that blockade of the renin-angiotensin system can confer retinoprotection in experimental models of diabetic retinopathy and ischemic retinopathy. This review examines the role of the renin-angiotensin system in diabetic retinopathy and the potential of its blockade as a treatment strategy for this vision-threatening disease.
Wilkinson-Berka
Jennifer L
JL
Department of Physiology, The University of Melbourne, Grattan St., Parkville, Vic., Australia. jlaberka@unimelb.edu.au
D000803:Angiotensin I / Q000494:pharmacology; D000804:Angiotensin II / Q000502:physiology*; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D030801:Animals, Genetically Modified; D003930:Diabetic Retinopathy / Q000097:blood / Q000209:etiology*; D006801:Humans; D006973:Hypertension / Q000150:complications; D009389:Neovascularization, Pathologic; D010446:Peptide Fragments / Q000494:pharmacology; D007703:Peptidyl-Dipeptidase A / Q000502:physiology; D012083:Renin / Q000235:genetics; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D012160:Retina / Q000473:pathology / Q000503:physiopathology / Q000648:ultrastructure
D010446:Peptide Fragments; D000804:Angiotensin II; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2; D012083:Renin; C118790:angiotensin I (1-7)