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Moe Aung, Moon Han, Han na Park, Jane Abey, Peter Thule, P Iuvone, Machelle Pardue; Role of Dopamine Deficiency in Visual Dysfunction in Early-stage Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1143.
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© ARVO (1962-2015); The Authors (2016-present)
Studies in diabetic patients and rodents consistently observe subtle deficits in vision prior to the onset of vasculopathy; however, the underlying causes remain unclear. At such early stages, disruption in the retinal dopaminergic system has also been found. As dopamine (DA) has recently been identified as crucial for visual function, the purpose of this study was to examine the role of DA deficiency in early visual defects in diabetic retinopathy (DR).
Hyperglycemia was induced in pigmented Long-Evans rats and C57BL/6 mice with STZ injection, a model of Type 1 diabetes mellitus. Diabetes was confirmed by serially elevated blood glucose (>250 mg/dl). Control and diabetic rats were sustained for either 4 weeks or 12 weeks to evaluate DA levels with HPLC. Visual function with optokinetic tracking of each rat was assessed at the end of the study. In addition, hyperglycemic mice were maintained for 8 weeks and then tested for the effects of acute DA receptor agonist treatments on visual function. All mice received i.p. injections of a dopamine D1-receptor agonist (SKF38393, 1mg/kg), vehicle, and a dopamine D4-receptor agonist (PD168077, 1mg/kg). Visual function was evaluated with optokinetic tracking beginning 30 min after each drug injection.
Significant reduction in DA level (25-30%) was observed in diabetic rats at both time-points (p<0.001). More importantly, changes in DA level correlated significantly with both visual acuity (r=-0.598, p=0.005) and contrast sensitivity (r=-0.648, p=0.002). Treatment with D1-receptor agonist significantly improved visual acuity of diabetic mice (p<0.01), but had no effect on contrast sensitivity. In contrast, treatment with D4-receptor agonist significantly enhanced only the contrast sensitivity of diabetic mice (p<0.05). Neither treatment restored visual function completely back to normal control levels.
Diabetes significantly reduced DA levels in STZ rat retinas, at similar time-points as previously reported onset of visual deficits (Aung et al, ARVO E-abstract 5960). DA deficiency may contribute to early visual dysfunction in diabetes. DA levels correlated significantly with visual dysfunction and acute treatment with DA receptor agonists improved vision in diabetic animals. Treatments aimed at restoring DA levels or preserving the dopaminergic system in the retina may provide therapeutic benefit for early-stage DR.
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