Abstract
Purpose :
Previously, we showed that daily L-DOPA treatment delayed visual and retinal defects in diabetic (DM) rats. We hypothesize that deficiency in retinal dopaminergic activity contributes to the changes in visual and retinal function observed in diabetic retinopathy. In addition to reproducing the protective effects of L-DOPA in diabetic rats on visual and retinal function, we demonstrate that L-DOPA treatment restores retinal dopamine and its metabolite DOPAC.
Methods :
Streptozotocin (STZ;100 mg/kg) was used to induce diabetes (blood glucose >250 mg/dl) in Long Evans rats. Rats were randomly assigned to Ctrl+Veh, Ctrl+L-DOPA, DM+L-DOPA or DM+Veh groups. Daily treatment began post-STZ after rats showed retinal and visual defects. L-DOPA treated rats were treated each morning with L-DOPA (10 mg/kg IP on first cohort, 20 mg/kg oral in future cohorts). Spatial frequency thresholds using optomotor response and retinal function using dark adapted electroretinograms (ERGs) were measured at baseline, 3, 6, and 10 weeks post-STZ. At 10 weeks post-STZ, retinal L-DOPA, dopamine, and DOPAC were measured via HPLC.
Results :
DM+L-DOPA rats had preserved spatial frequency thresholds compared to DM+Veh rats after the onset of treatment at 6 and 10 weeks post-STZ (p = 0.0013). ERG OP1 implicit times were delayed in DM+Veh rats and worsened at 6 and 10-weeks post-STZ (Figure). DM+L-DOPA rats showed delayed OP1 implicit times at 3 weeks that recovered at 6 and 10-weeks post-STZ. At 10 weeks post-STZ, DM+Veh rats showed a 19.56% reduction in retinal dopamine compared to Ctrl+Veh rats, while L-DOPA treated rats had elevated dopamine and DOPAC levels compared to Ctrl+Veh rats.
Conclusions :
These results confirmed our previous findings that L-DOPA treatment starting at the onset of visual defects protects from further visual decline and restores retinal function in diabetic rats. Daily L-DOPA treatment also ameliorated the reduction in retinal dopamine in diabetic rats. These data support that dopamine deficiency contributes to the pathophysiology of diabetic retinopathy and suggests that L-DOPA treatment may be efficacious in the early stages of disease to restore retinal dopamine and protect from retinopathy.
This is a 2020 ARVO Annual Meeting abstract.