Evidence of decreased dopamine receptor‐mediated control of gap junction coupling in the inner nuclear layer of the diabetic Ins2Akita mouse retina (1129.1)

Abstract

Dopamine (DA) is a light‐adaptive factor that plays an important role in daytime vision. DA controls the gain of retinal signal transmission partly by controlling gap junction coupling of retinal neurons. Because preliminary data suggests that DA levels are lower in the diabetic Ins2Akita mouse retina, we hypothesized that gap junction coupling would be altered in diabetic retina. We assayed coupling using a “cut‐loading” technique, in which whole‐mounted retinas are cut with a razor dipped in gap junction‐permeable tracer Neurobiotin (NB) and quantified NB‐labeled cells in the inner nuclear layer (INL) using fluorescence microscopy. Experiments were performed under dark‐adapted conditions. The extent of coupling in control (C57Bl6) retinas was tested in the presence of the D2‐like receptor (D2R) agonist quinpirole, the D2R antagonist sulpiride, or the gap junction antagonist beta‐glycyrrhizic acid (BGA). As expected, D2R activation and BGA reduced gap junction coupling of the NB‐labeled cells in the INL, while D2R antagonism increased tracer coupling. In the diabetic Ins2Akita mice, we found that neurons in the INL showed increased tracer coupling compared to non‐diabetic littermates. We propose that this increase in gap junction coupling between retinal neurons reflects a decrease in DA levels. Decreased DA levels and an altered coupling state of retinal neurons may be hallmarks of diabetic retinasGrant Funding Source: Supported by American Heart Association (12BGIA12040362)