Biology subjects

Eggers, E.

Publications and source records attributed to Eggers, E..

2 recordsLinked to original sources

bioRxiv2025

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.

neuroscience↗

bioRxiv2020

Impaired light adaptation of ON-sustained ganglion cells in early diabetes is attributable to diminished dopamine D4 receptor sensitivity

Purpose: It has been known for some time that normal retinal signaling is disrupted early on in diabetes, before the onset of the vascular pathologies associated with diabetic retinopathy. There is growing evidence that levels of retinal dopamine, a neuromodulator that mediates light adaptation, may also be reduced in early diabetes. Previously, we have shown that after six weeks of diabetes in a mouse model, light adaptation is impaired at the level of ON-sustained (ON-s) ganglion cells. The purpose of this study was to determine whether changes in dopamine receptor sensitivity contribute to this dysfunction. Here we used single cell retinal patch-clamp recordings from the mouse retina to determine how activating dopamine type D4 receptors (D4Rs) changes the light-evoked and spontaneous excitatory inputs to ON-s ganglion cells, in both control and diabetic animals. We also used in-situ fluorescent hybridization to assess whether D4R expression was impacted by diabetes. We found that D4R activation had a smaller impact on light-evoked excitatory inputs to ON-s ganglion cells in diabetic retinas compared to controls. This impaired D4R signaling is not attributable to a decline in D4R expression, as we found increased D4R mRNA density in the outer plexiform layer in diabetic retinas. This suggests that the cellular machinery of dopaminergic signaling is itself disrupted in early diabetes and may be amenable to chronic dopamine supplementation therapy.

neuroscience↗