Abstract
Purpose :
Levodopa restores retinal dopamine levels in diabetic retinopathy and ameliorates retinal dysfunction in both rodent models and clinical studies. However, these studies involved short-term treatment prior to the onset of retinal vascular defects. In this study, we evaluated the protective effect of levodopa treatment in later stages of DR in a diabetic rat model when started after detection of early retinal dysfunction.
Methods :
Hyperglycemia (≥250 mg/dL) was induced in a subset of 2-month-old male Long Evans rats via streptozotocin (STZ) injection (100 mg/kg). Oral administration of levodopa (10 mg/kg levodopa, 2.5 mg/kg carbidopa, 0.8 g/kg powdered peanut butter dissolved in 1:1 water) or peanut butter vehicle (0.8 g/kg powdered peanut butter in 1:1 water) for 5 days per week began at 6 weeks post-STZ injection and continued until 24 weeks post-STZ injection. Rats were assessed with full-field electroretinogram and optomotor response prior to STZ injection and for every 4 weeks following hyperglycemia. Mixed-effects linear regressions were used to compare the effect of diabetes and levodopa treatment on outcome measures.
Results :
Levodopa treatment improved spatial frequency thresholds in diabetic rodents (n=9) relative to vehicle-treated diabetic rodents (n=9) by 30% (at 24 weeks post-STZ injection, 0.390±0.008 vs. 0.298±0.008 c/d, p<0.001). Levodopa similarly improved contrast sensitivity thresholds in diabetic rodents by 35% during treatment period (at 24 weeks post-STZ, 5.018±0.217 vs. 3.212±0.139 a.u., p=0.004). In response to dim stimuli, dark-adapted, levodopa-treated diabetic rodents had improved oscillatory potential delays compared to vehicle-treated rodents at 24 weeks post-STZ injection (57.72±1.09 vs. 67.50±2.53 ms, p=0.008). Oscillatory potential delays in response to dark-adapted bright stimuli were worsened by diabetes but were not improved with levodopa treatment.
Conclusions :
Levodopa maintained its protective effect on retinal and visual function to 24 weeks post-STZ when vascular defects are present in the STZ-induced diabetic rat. Future work will look at vascular biomarkers to evaluate the effect of dopaminergic treatment on vascular defects in DR.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.