Dopamine Deficiency Contributes to Early Visual Dysfunction in a Rodent Model of Type 1 Diabetes

• Type of Material: Article
• Authors: Moe H. Aung, Emory University; Han na Park, Emory University; Moon K. Han, Emory University; Tracy S. Obertone, Emory University; Jane Abey, Emory University; Fazila Aseem, Emory University; Peter M. Thule, Emory University; P Michael Iuvone, Emory University; Machelle Pardue, Emory University
• Language: English
• Date: 2014-01-15
• Publisher: Society for Neuroscience
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2014 the authors 0270-6474/14/340726-11
• Final Published Version (URL): http://www.jneurosci.org/content/34/3/726
• Title of Journal or Parent Work: Journal of Neuroscience Nursing
• ISSN: 0270-6474
• Volume: 34
• Issue: 3
• Start Page: 726
• End Page: 736
• Grant/Funding Information: This work was supported by the National Institutes of Health (NIH Grants P30 EY006360 and R01 EY004864 to P.M.I. and National Institute of Diabetes and Digestive and Kidney Diseases Grant RO1 DK07601-01 to P.M.T.); the Department of Veterans Affairs (Rehabilitation R&D Service Merit Award and Research Career Scientist Award to M.T.P. and Biological Laboratory R&D Service Merit Award to P.M.T.); Research to Prevent Blindness (Departmental Award); the Juvenile Diabetes Research Foundation (Research Grant and Innovative Award to P.M.T.); and the Children's Healthcare of Atlanta Research Center (Award to P.M.T.).
• Keywords: Dopamine; Visual function; Diabetic retinopathy
• Research Categories: Health Sciences, Pathology; Health Sciences, Opthamology; Health Sciences, Mental Health

Abstract

Dopamine (DA) functions as an essential neuromodulator in the brain and retina such that disruptions in the dopaminergic system are associated with common neurologic disorders such as Parkinson's disease. Although a reduction in DA content has been observed in diabetes, its effects in the development of diabetes-induced neuropathy remains unknown. Because the retina is rich in DA and has a well known diabetes-induced pathology (diabetic retinopathy or DR), this study was designed to examine the role of retinal DA deficiency in early visual defects in DR. Using rodent models of type 1 diabetes mellitus, we investigated whether diabetes caused a reduction in retinal DA content in both rats and mice and determined whether restoring DA levels or activating specific DA receptor pathways could improve visual function (evaluated with optokinetic tracking response) of diabetic mice, potentially via improvement of retinal function (assessed with electroretinography). We found that diabetes significantly reduced DA levels by 4 weeks in rats and by 5 weeks in mice, coincident with the initial detection of visual deficits. Treatment with l-DOPA, a DA precursor, improved overall retinal and visual functions in diabetic mice and acute treatment with DA D1 or D4 receptor agonists improved spatial frequency threshold or contrast sensitivity, respectively. Together, our results indicate that retinal DA deficiency is an underlying mechanism for early, diabetes-induced visual dysfunction and suggest that therapies targeting the retinal dopaminergic system may be beneficial in early-stage DR.