title: Dopamine deficiency contributes to early visual dysfunction in a rodent model of type 1 diabetes.
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.
authors.affiliation: Department of Neuroscience, Department of Ophthalmology, Department of Endocrinology, and Department of Pharmacology, Emory University, Atlanta, Georgia 30322, and Rehab R&D Center of Excellence and Biomedical Laboratory Research and Development, Atlanta VA Medical Center, Atlanta, Georgia 30033.
authors.forename: Moe H
authors.initials: MH
authors.lastname: Aung
authors.forename: Han Na
authors.initials: HN
authors.lastname: Park
authors.forename: Moon K
authors.initials: MK
authors.lastname: Han
authors.forename: Tracy S
authors.initials: TS
authors.lastname: Obertone
authors.forename: Jane
authors.initials: J
authors.lastname: Abey
authors.forename: Fazila
authors.initials: F
authors.lastname: Aseem
authors.forename: Peter M
authors.initials: PM
authors.lastname: Thule
authors.forename: P Michael
authors.initials: PM
authors.lastname: Iuvone
authors.forename: Machelle T
authors.initials: MT
authors.lastname: Pardue
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000378:metabolism*; D003930:Diabetic Retinopathy / Q000188:drug therapy / Q000378:metabolism*; D004195:Disease Models, Animal; D004298:Dopamine / Q000172:deficiency*; D005260:Female; D007980:Levodopa / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D051381:Rats; D020318:Rats, Long-Evans; D012160:Retina / Q000187:drug effects / Q000378:metabolism*
chemical_list: D007980:Levodopa; D004298:Dopamine
keywords: Diabetic retinopathy; Dopamine; Visual function