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Kyle Chesler, Cara Motz, Rachael S Allen, P. Michael Iuvone, Machelle T Pardue; Clinically relevant timing of L-DOPA treatment in diabetic rats slows the progression of retinopathy. Invest. Ophthalmol. Vis. Sci. 2019;60(9):5972.
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© ARVO (1962-2015); The Authors (2016-present)
Previous studies have demonstrated that daily L-DOPA treatment preserves retinal and visual function in diabetic (DM) rats. These studies started L-DOPA treatments at the onset of diabetes and therefore offer limited clinical translatability - it is more likely that drugs for diabetic retinopathy (DR) would be prescribed when retinal and visual deficits are detectable. Here, we investigate the efficacy of L-DOPA treatment to preserve visual, retinal, and vascular function in diabetic rats when treatment was started after the appearance of visual and retinal defects.
Hyperglycemia was induced in male pigmented Long Evans rats with streptozotocin (STZ;100 mg/kg; blood glucose >250 mg/dl). At 3 weeks post-STZ, rats showed retinal and visual deficits and began daily treatments. Rats were randomly assigned into four groups: Ctrl+Veh, Ctrl+L-DOPA, DM+L-DOPA and DM+Veh. L-DOPA treated rats were injected each morning with 10 mg/kg L-DOPA and 2.5 mg/kg carbidopa in a 1:10 DMSO-Saline vehicle. Spatial frequency thresholds using optomotor response and retinal function using dark and light-adapted electroretinograms were measured at pre-STZ baseline, 3, 6, and 10 weeks post-STZ. Retinal functional hyperemia was assessed using green flickering light (530 nm; 12 Hz) induced vasodilation at 6 and 10-weeks post-STZ.
DM+L-DOPA rats showed preserved spatial frequency thresholds compared to DM+Veh rats after the onset of treatment. OP1 implicit times were delayed in DM+Veh rats and became progressively more delayed at 6 and 10-weeks post-STZ. DM+L-DOPA rats showed delayed OP1 implicit times at 3 weeks at the onset of treatment that worsened at 6-weeks, but trended towards recovery by 10-weeks. While there were no differences in flicker-induced vasodilation between DM+Veh versus Ctrl rats, DM+L-DOPA rats showed greater flicker induced arteriole vasodilation than all other groups at 6 and 10 weeks post-STZ.
L-DOPA treatments started at the first signs of dysfunction in STZ-induced diabetic rats protected from further spatial frequency declines, maintained retinal function, and enhanced neurovascular function. Taken together, these results complement previous findings that L-DOPA is protective against DR and suggest that starting L-DOPA treatment even after measurable vision loss may slow the progression of visual deficits.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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