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Victoria P Connaughton, Mikayla Crowley-Perry, Allison Murk, Terry Davidson, Cassie Rowe; Using zebrafish to investigate hyperglycemia-induced molecular and behavioral changes to visual circuits. Invest. Ophthalmol. Vis. Sci. 2020;61(7):300.
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Hyperglycemia carries the risk of long-term complications due to vascular damage. We assessed two such complications, diabetic retinopathy and dementia, to determine if there is a correlation between changes in retina and brain.
Chronic hyperglycemia, induced using the alternate immersion protocol, was maintained in adult zebrafish for 4wks or 8wks, at which time behavioral and molecular changes were assessed. Cognitive changes were determined using a three-chamber choice associative learning task with a live shoal reinforcer; an established optomotor response (OMR) protocol assessed visually-guided behaviors. Following behavioral assessment, tissue was collected to identify differences among inflammatory and neurochemical protein levels using western blots.
After 4wks, glucose-treated fish displayed an impaired ability to learn and maintain memory with an increase in the number of force-rewarded trials, a ~20% decrease in the number of high performing fish on the first day of reversal, and a decreased discrimination ratio. These changes were correlated with a decrease in tight junction proteins and an increase in inflammatory markers (NF-κB, IKK) in both brain and retina. At 8wks, initial behavioral analyses revealed dampened effects of glucose that were either comparable to controls or due to osmotic effects. However, examining the data based on fish performance (i.e., high vs. low performing), revealed a glucose-specific effect on discrimination ratio in the high performing group. Inflammatory markers in brain were still elevated at 8wks, as were levels of TH and GAD. However, there were no changes in retinal tight junction markers, though levels of TH and Nf-KB were upregulated. Glucose-treated fish performed better on the OMR at both time points relative to controls.
There are differential sensitivities to glucose by individual fish. Hyperglycemia-induced changes in brain and retina occur after 4wk of treatment, whereas tissue-specific effects are evident after 8wk.
This is a 2020 ARVO Annual Meeting abstract.
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