Abstract
Purpose :
Previous work has shown that dopamine 1 and 4 receptor (D1R, D4R) agonists selectively enhance spatial frequency and contrast sensitivity thresholds in mice, respectively (Jackson et al., J Neurosci 2012). Furthermore, similar differential effects were found in partially restoring visual deficits in diabetic mice (Aung et al., J Neurosci 2014). In this study, we investigated the selective benefits of D1R, D2R, and D4R agonists on spatial frequency and contrast sensitivity thresholds in a rat model of Type I diabetes.
Methods :
Streptozotocin (STZ) was used to induce hyperglycemia in 2-month-old male Long–Evans rats. The experimental design consisted of performing optomotor response (OMR) assessments in diabetic rats (n=6) and control rats (n=6) at 8 weeks post-STZ. Spatial frequency and contrast sensitivity thresholds were measured before and 30 minutes after a single intraperitoneal dose of SKF38393 hydrobromide, a dopamine D1R agonist (1 mg/kg); Bromocriptine mesylate, a dopamine D2R agonist (5 mg/kg); or PD168077 maleate, a dopamine D4R agonist (1 mg/kg). Each agonist was injected 2-3 days apart. Data was analyzed as change from baseline with two-way repeated ANOVAs to compare differences between agonists.
Results :
Spatial frequency thresholds were significantly restored with the D1R agonist for diabetic rats (9.6%, p<0.001), but not for control rats (1.4%; Figure). Contrast sensitivity thresholds were restored with D4R agonist for diabetic rats (8.2%, p<0.05) and control rats (1.8%, p<0.05) and showed a trend for restoration with D2R agonists in diabetic rats (5.7%) compared with D1R (1.0%).
Conclusions :
These results confirm the selective nature of D1R and D4R agonists on spatial frequency and contrast sensitivity, respectively, and show that these effects are preserved in early stage diabetes. We also find that the D2R agonist selectively enhances contrast sensitivity. Based on these findings, dopamine signaling appears fully functional at this stage of diabetes. Future experiments will determine how long dopamine signaling is intact in the progression of DR. Dopamine receptor agonists may provide a protective therapy for visual deficits in DR.
This is a 2020 ARVO Annual Meeting abstract.