Abstract
Purpose :
Dopamine (DA) is an essential neuromodulator in the retina and reduction of DA has been observed in early diabetes. How diabetes affects specific dopaminergic signaling pathways in the retina is not clear. We hypothesize the addition of selective dopamine D1 (D1R) and D4 (D4R) receptor agonists will modify amplitude and timing in light-evoked whole retina electroretinogram (ERG) recordings.
Methods :
Control (citrate injected, N=12) and diabetic (streptozotocin injected, N=13) mice were dark adapted overnight 6 weeks after injections. Retinas were dissected, placed in an ex vivo ERG and perfused with oxygenated Ringer’s solution. Light-evoked whole retina responses were recorded before and after perfusion with a D4R agonist, 500nM PD-168077-maleate (PD, N=12) or D1R agonist, 20 µM SKF-38393 (SKF, N=13). Two-way repeated measures ANOVAs using Student-Newman-Keuls pairwise comparisons in SigmaPlot were performed to compare amplitude and time to peaks. RNAscope labeling of mRNA for D1Rs and D4Rs was performed on 5 µm thick retinal slices.
Results :
After PD treatment, there was a significant decrease in A-wave amplitude (p=0.006) and B-wave amplitude (p=0.014) and a significant increase in the B-wave implicit time (p=0.019) and rise time (p=0.013) in the control group. In contrast, there were no significant changes in the diabetic group. Comparing control and diabetic groups after PD treatment, there were significant differences in B-wave amplitude (p=0.014), B-wave implicit time (p=0.016) and rise time (p=0.013). After SKF treatment, there was a significant increase (p=0.048) in rise time for the control group, but not for the diabetic group. There were no significance differences between the amplitude or implicit times of either wave. D1R labeling was found mainly in the INL with some in GCL. D4R labeling was found mainly in the ONL with some in the INL. There was no significant difference between control and diabetic for either D1R or D4R labeling.
Conclusions :
These results are consistent with the hypothesis showing D1R and D4R agonists will modify the light-evoked whole retina ERG responses. Interestingly, the results indicate D1Rs and D4Rs are less effective in diabetic retinas, not likely from lower receptor expression levels, but potentially due to loss of dopamine. Further experiments will explore how diabetes affects the specific dopaminergic signaling pathways within the retina.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.