Dopamine Deficiency Contributes to Early Visual Dysfunction in a Rodent Model of Type 1 Diabetes
Dopamine Deficiency Contributes to Early Visual Dysfunction in a Rodent Model of Type 1 Diabetes
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DOI：
10.1523/jneurosci.3483-13.2014
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发表时间：
2014-01-15
影响因子：
5.3
通讯作者：
Pardue, Machelle T.
中科院分区：
文献类型：
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作者：
Aung, Moe H.;Park, Han Na;Pardue, Machelle T.
多巴胺（DA）作为脑和视网膜中的必需神经调节剂起作用，使得多巴胺能系统中的破坏与常见的神经系统障碍如帕金森病相关。虽然在糖尿病中观察到DA含量减少，但其在糖尿病诱导的神经病变发展中的作用仍然未知。因为视网膜富含DA，并且具有众所周知的糖尿病诱导的病理（糖尿病视网膜病变或DR），本研究旨在检查视网膜DA缺乏在DR中的早期视觉缺陷中的作用。使用1型糖尿病的啮齿动物模型，我们研究了糖尿病是否引起大鼠和小鼠视网膜DA含量的减少，并确定了恢复DA水平或激活特异性DA受体这些通路可以潜在地通过改善视网膜功能（用视网膜电图评估）来改善糖尿病小鼠的视觉功能（用视动追踪反应评估）。我们发现，糖尿病在大鼠中4周和小鼠中5周显著降低了DA水平，与最初检测到的视觉缺陷一致。用L-DOPA（DA前体）治疗改善了糖尿病小鼠的整体视网膜和视觉功能，并且用DA D1或D4受体激动剂急性治疗分别改善了空间频率阈值或对比敏感度。总之，我们的研究结果表明，视网膜DA缺乏是早期糖尿病诱导的视觉功能障碍的潜在机制，并表明针对视网膜多巴胺能系统的治疗可能对早期DR有益。
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.