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Diabetes 55:2401-2411, 2006
DOI: 10.2337/db05-1635
© 2006 by the American Diabetes Association
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Perspectives in Diabetes

Diabetic Retinopathy

Seeing Beyond Glucose-Induced Microvascular Disease

David A. Antonetti1,2, Alistair J. Barber1,2, Sarah K. Bronson1, Willard M. Freeman1, Thomas W. Gardner1,2, Leonard S. Jefferson1, Mark Kester4, Scot R. Kimball1, J. Kyle Krady3, Kathryn F. LaNoue1, Christopher C. Norbury1, Patrick G. Quinn1, Lakshman Sandirasegarane4, Ian A. Simpson3 for the JDRF Diabetic Retinopathy Center Group

1 Department of Cellular and Molecular Physiology, Penn State College of Medicine, Hershey, Pennsylvania
2 Department of Ophthalmology, Penn State College of Medicine, Hershey, Pennsylvania
3 Department of Neural and Behavioral Sciences, Penn State College of Medicine, Hershey, Pennsylvania
4 Department of Pharmacology, Penn State College of Medicine, Hershey, Pennsylvania

Address correspondence and reprint requests to Thomas W. Gardner, Departments of Ophthalmology and Cellular & Molecular Physiology, Penn State College of Medicine, 500 University Dr., HU19, Hershey, PA 17033. E-mail: tgardner{at}psu.edu

Abbreviations: DCCT, Diabetes Control and Complications Trial; IRS, insulin receptor substrate; PI, phosphatidylinositol; PKC, protein kinase C; VEGF, vascular endothelial growth factor

Diabetic retinopathy remains a frightening prospect to patients and frustrates physicians. Destruction of damaged retina by photocoagulation remains the primary treatment nearly 50 years after its introduction. The diabetes pandemic requires new approaches to understand the pathophysiology and improve the detection, prevention, and treatment of retinopathy. This perspective considers how the unique anatomy and physiology of the retina may predispose it to the metabolic stresses of diabetes. The roles of neural retinal alterations and impaired retinal insulin action in the pathogenesis of early retinopathy and the mechanisms of vision loss are emphasized. Potential means to overcome limitations of current animal models and diagnostic testing are also presented with the goal of accelerating therapies to manage retinopathy in the face of ongoing diabetes.


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