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Lidia Cardelle, Rachael S Allen, Kyle Chesler, Machelle T Pardue; Dopamine Receptor Agonists Selectively Benefit Visual Deficits at Early Stages of Diabetic Retinopathy in Rats. Invest. Ophthalmol. Vis. Sci. 2021;62(8):3136.
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© ARVO (1962-2015); The Authors (2016-present)
Treating healthy and diabetic mice with dopamine receptor agonists selectively enhanced visual function; the D1R agonist increased spatial frequency thresholds, while the D4R agonist increased contrast sensitivity thresholds (Jackson et al., J Neurosci 2012; Aung et al., J Neurosci 2014). Here we investigated the benefits of three dopamine receptor agonists (D1R, D2R, D4R) on visual function at various stages of diabetic retinopathy (DR) in rats.
Hyperglycemia was induced in 2-month-old male Long–Evans rats using streptozotocin (STZ; blood glucose > 250 mg/dL). Optomotor responses (OMR) were measured in diabetic and control rats before and 30 minutes after a single intraperitoneal injection 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. OMR was assessed at 8 weeks post-STZ (n=10-11/group) and at 16 and 20 weeks post-STZ in a subset of rats (n=4-6/group). OMR thresholds were compared pre- and post-agonist between diabetic and control rats at 8 weeks post-STZ and then all agonists compared across time using three-way repeated ANOVAs.
At all timepoints, spatial frequency and contrast sensitivity thresholds were significantly decreased in diabetic rats (p<0.0001; Figure). At 8 weeks post-STZ, the D1R agonist selectively increased spatial frequency thresholds in diabetic rats (p<0.0001), but not in control rats. Additionally, the D4R agonist selectively increased contrast sensitivity thresholds in diabetic rats (p=0.0003) but not in control rats. These differences were not detectable at 16 or 20 weeks post-STZ. The D2R agonist did not show significant effects at any timepoint.
These results show that acute dosing of the D1R agonist selectively benefits visual acuity, while D4R selectively benefits contrast sensitivity at early stages of DR. Therefore, dopamine receptor agonists may benefit visual deficits associated with diabetes if they are administered early in disease progression.
This is a 2021 ARVO Annual Meeting abstract.
Baseline and post-agonist spatial frequency (left) and contrast sensitivity (right) thresholds at 8 weeks post-STZ demonstrate selective benefit with D1R and D4R agonists for diabetic rats, respectively. Results expressed as mean ± SEM. ****p<0.0001; ***p<0.001.
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