D1R- and D4R-Dependent Regulation of Retinal Light Adaptation in Diabetes

Diabetic retinopathy (DR) is considered a neurovascular disease, and key clinical features show impairments in visual acuity and electroretinogram (ERG) recordings. Dopamine, a critical regulator of light adaptation, is also reduced in diabetes and supplementation of dopamine or injection of dopamine agonists improve visual deficits in diabetic rodents and humans. We sought to examine how blocking D4Rs and D1Rs would affect ERG signaling in 6-week diabetic rodents. Blocking D4Rs with L745,870 significantly reduced dark-adapted A-wave amplitude in DM, but not non-DM retinas, with no change in a-wave implicit timing, suggesting diabetic alterations in D4R signaling in photoreceptors. Light-adapted (LA) recordings revealed blocking D4Rs significantly increased A-wave amplitude and delayed A-wave implicit timing in DM and non-DM retinas. B-wave amplitudes were elevated at the highest flash intensity, and rise time was significantly faster, indicating an inability to adjust to background light. D1R blockade with SCH-23390 had little effect on ERG recordings for both groups, aside from increased B-wave amplitude and delayed rise time in dark-adapted DM conditions towards the lower light intensities. While small, D4R blockade seems to have a bigger effect in DM conditions during light adaptation, suggesting that diabetes impairs the retinas ability to adjust to light adaptation. These studies show that dopamine signaling in diabetes is perturbed and an important avenue for future investigation.