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Rachael S Allen, Amy L. Ottensmeyer, Adam Hanif, Curran Sidhu, Li He, P. Michael Iuvone, Peter Thule, Machelle T Pardue; Retinal deficits precede cognitive and motor deficits in a rat model of Type II diabetes. Invest. Ophthalmol. Vis. Sci. 201657(12):.
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© ARVO (1962-2015); The Authors (2016-present)
Diabetic retinopathy is the leading cause of blindness in working age adults and is likely intimately related to other diabetic complications, for example, cognitive decline and microvascular changes in the brain. The Goto-Kakizaki (GK) rat is a spontaneous, polygenic, non-obese model of Type II diabetes. Animals typically develop impaired glucose-induced insulin secretion by 2 weeks and hyperglycemia by 4 weeks. While retinal, cognitive, and motor deficits have been identified in GK rats, the temporal relationship between these deficits has not been investigated. We hypothesized that retinal changes precede cognitive and motor deficits in GK rats.
We assessed retinal function via electoretinograms (ERG), motor function using the rotarod, and hyperglycemia and insulin resistance via glucose and insulin tolerance tests in male and female GK rats and Wistar controls at 4 and 8 weeks of age. Spatial alternation (cognitive function) and exploratory motor behavior were assessed using a Y-maze task at 5, 6, 7, and 8 weeks.
GK rats exhibited significant hyperglycemia (p < 0.001) and insulin resistance (p < 0.001) by 4 weeks of age. Retinal deficits were also observed in GK rats by 4 weeks, including delays in ERG implicit times (flicker, p < 0.01; b-wave, p < 0.001; oscillatory potentials, p < 0.001). Additionally, GK rats showed increased (above control) ERG amplitudes for a- wave, b- wave, oscillatory potential, and flicker at 4 weeks (p < 0.001 for each) that reverted toward values observed in Wistar controls by 8 weeks. GK rats exhibited deficits in cognitive function beginning at 6 weeks (p < 0.05) and in exploratory motor behavior beginning at 7 weeks (p < 0.05). However, no deficits on rotarod were observed, though a trend for reduced latency was observed in GK rats at 8 weeks. Flicker ERG delays correlated with cognitive deficits in male GK rats at 8 weeks (R2 = 0.625, p < 0.001).
In GK rats, retinal function deficits developed prior to cognitive or motor deficits. Future studies will investigate common mechanistic links between these findings, such as loss of dopamine, and determine if retinal deficits can predict cognitive and motor dysfunction.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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