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World J Diabetes. May 15, 2010; 1(2): 57-64
Published online May 15, 2010. doi: 10.4239/wjd.v1.i2.57
Neurodegeneration: An early event of diabetic retinopathy
Marta Villarroel, Andreea Ciudin, Cristina Hernández, Rafael Simó
Marta Villarroel, Andreea Ciudin, Cristina Hernández, Rafael Simó, Diabetes and Metabolism Research Unit. Institut de Recerca Hospital Universitari Vall D’Hebron, Universitat Autònoma de Barcelona, Barcelona 08035, Spain
Marta Villarroel, Cristina Hernández, Rafael Simó, CIBER for Diabetes and Associated Metabolic Diseases (CIBERDEM, Instituto de Salut Carlos III), Barcelona, Spain
Author contributions: Villarroel M and Ciudin A were responsible for the bibliographic research; Hernández C and Simó R prepared the first draft of the review; The final version of the paper was corrected and approved by all the authors.
Supported by Grants from the Ministerio de Ciencia e Innovacion, No. SAF2009-07408, CIBER de Diabetes y Enfermedades Metabólicas Asociadas and Generaltitat de Catalunya, No. 2009SGR739
Correspondence to: Rafael Simó, MD, PhD, Associate Professor, Diabetes Research Unit, Institut de Recerca Hospital Universitari Vall d’Hebron, Pg. Vall d’Hebron 119-129, Barcelona 08035, Spain.
Telephone: +34-93-4894172 Fax: +34-93-4894032
Received: October 9, 2009
Revised: March 3, 2010
Accepted: March 10, 2010
Published online: May 15, 2010

Diabetic retinopathy (DR) has been classically considered to be a microcirculatory disease of the retina caused by the deleterious metabolic effects of hyperglycemia per se and the metabolic pathways triggered by hyperglycemia. However, retinal neurodegeneration is already present before any microcirculatory abnormalities can be detected in ophthalmoscopic examination. In other words, retinal neurodegeneration is an early event in the pathogenesis of DR which predates and participates in the microcirculatory abnormalities that occur in DR. Therefore, the study of the mechanisms that lead to neurodegeneration will be essential to identify new therapeutic targets in the early stages of DR. Elevated levels of glutamate and the overexpression of the renin- angiotensin-system play an essential role in the neurodegenerative process that occurs in diabetic retina. Among neuroprotective factors, pigment epithelial derived factor, somatostatin and erythropoietin seem to be the most relevant and these will be considered in this review. Nevertheless, it should be noted that the balance between neurotoxic and neuroprotective factors rather than levels of neurotoxic factors alone will determine the presence or absence of retinal neurodegeneration in the diabetic eye. New strategies, based on either the delivery of neuroprotective agents or the blockade of neurotoxic factors, are currently being tested in experimental models and in clinical pilot studies. Whether these novel therapies will eventually supplement or prevent the need for laser photocoagulation or vitrectomy awaits the results of additional clinical research.

Keywords: Diabetic retinopathy, Angiotensin II, Erythropoietin, Glutamate, Retinal neurodegeneration, Neuropeptides, Pigment epithelial derived factor, Somatostatin