Purchase this article with an account.
Ivy S Samuels, Janet C. Peachey, Parastoo Bassiri, Lindsey A Ebke, Brent A Bell; Diabetes-induced c-wave reductions are independent of the Müller glia-generated Kir4.1-mediated [K+] conductance and are correlated with elevated GLUT1 levels.. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4293.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
The c-wave is generated by the summation of a hyperpolarization of the RPE apical membrane driven by a lowering of [K+] and a negative Kir4.1-mediated slow PIII response of the Müller glia cells. Both RPE and Müller glia exhibit functional defects quickly after onset of hyperglycemia in mouse models of diabetes. The purpose of this study is to determine the if the reduction to the c-wave observed in mouse models of Type 1 diabetes is due to an increased [K+] conductance generated by the Müller glia.
We measured the Müller glia generated slow PIII ERG component in Nyxnob mice that lack the ERG b-wave. Nyxnob mice were made diabetic by streptozotocin (STZ) injection or received vehicle as a control. After 1, 2 and 4 weeks of sustained hyperglycemia (>250mg/dl), standard strobe flash electroretinography and dc-ERG testing were conducted. Histological analysis and in vivo imaging was performed. ARPE-19 cells were grown in high and low glucose conditions and treated with insulin for 3 days. Western blotting and immunofluorescence microscopy was performed.
Slow PIII amplitudes were significantly reduced in mice with STZ-induced Type 1 diabetes at 2 weeks of hyperglycemia (p<0.05, n≥4). The amplitudes were reduced to a greater extent than the a-wave at each time point, and slow PIII defects were identified before photoreceptor activity was decreased. Significant reductions to the c-wave amplitudes were correlated with increased GLUT1 on the basolateral membrane. When grown in high glucose, ARPE-19 cells showed a similar increase in GLUT1.
Diabetic Nyxnob mice display reductions in the c-wave and slow PIII that appear earlier, and more severe than for the a-wave. Because the c-wave and slow PIII are both reduced, the c-wave reduction cannot be attributed to an increase in the Muller glia derived K+ conductance. Furthermore, because the a-wave, slow PIII and c-wave reductions were not equivalent, they were not a result of a general change in membrane resistance. These data demonstrate a functional change within RPE cells as a result of hyperglycemia.
This PDF is available to Subscribers Only