期刊
JOURNAL OF NEUROSCIENCE
卷 34, 期 3, 页码 726-736出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.3483-13.2014
关键词
Diabetic retinopathy; Dopamine; Visual function
资金
- National Institutes of Health (NIH) [P30 EY006360, R01 EY004864]
- National Institute of Diabetes and Digestive and Kidney Diseases Grant [RO1 DK07601-01]
- Department of Veterans Affairs (Rehabilitation R&D Service Merit Award)
- Research to Prevent Blindness (Departmental Award)
- Juvenile Diabetes Research Foundation
- Children's Healthcare of Atlanta Research Center
- Department of Veterans Affairs (Research Career Scientist Award)
- Department of Veterans Affairs (Biological Laboratory R&D Service Merit Award)
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.
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