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Divya Narayanan, Nikolay Akimov, Eric Muir, Timothy Q Duong, Rene C Renteria; Effect of Moderate Hypercapnic Challenge on Focal Electroretinogram in the Ins2Akita Mouse Model of Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):488.
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© ARVO (1962-2015); The Authors (2016-present)
Previous studies have shown that relatively severe hypercapnia (i.e., high plasma PCO2) can compromise full-field electroretinogram (ERG) responses in normal animals. We hypothesized that the heterozygous Ins2Akita mouse model of diabetes, which develops retinopathy, will exhibit greater vulnerability to hypercapnia than normal controls. Here, we assessed the effect of a moderate hypercapnic challenge on focal ERG responses in diabetic Akita mice.
Focal ERGs were recorded for seven stimulus intensities (range: 0.0004 to 363 cds/m2)using a spot size of 1.5mm and flash duration of 4ms, (Micron III, Phoenix Research Labs) from 8 diabetic (aged 7.3±0.5 mos) and 5 C57Bl6J wild-type (WT) (aged 6.1±0.1 mos) mice, under two conditions: 1) inhalation of regular room air and 2) hypercapnic challenge (5% CO2, 21% O2, balance N2). Both were delivered through a nose cone with 1.5% isoflurane to keep the mice anesthetized. Amplitude and implicit time (IT) for a-wave and b-wave were calculated. Each animal’s b-wave intensity-response data were fit with a Naka-Rushton function to compare Vmax (maximum amplitude), slope, and I1/2 (half-saturating intensity).
In WT mice, half-saturating intensity (I1/2) trended smaller but was not significantly different between inhalation conditions (1.5±0.4 cds/m2 hypercapnia vs. 2.6±0.6 cds/m2 room air, p=0.054).In diabetic mice, however, I1/2 was significantly reduced during hypercapnic challenge (1.3±0.2 cds/m2 hypercapnia vs. 2.3±0.4 cds/m2 room air, p=0.001). Responses from both WT and diabetic mice showed no difference in Vmax or slope during hypercapnia. Diabetic mice had significantly reduced b-wave amplitudes compared to WT in both room air (Vmax=150±24 µV in Akita and 244±21 in WT, p=0.02) and during hypercapnia (Vmax=146±21 µV in Akita and 245±19 in WT, p=0.009). A-wave amplitudes and a- and b-wave ITs were not significantly different between Akita and WT groups.
Our results suggest that moderate hypercapnia with 5% CO2 renders a low-level challenge on mice and hence did not significantly alter FERG responses in the WT group. In diabetic Akita, moderate hypercapnic challenge caused a greater alteration in retinal neuronal sensitivity than in WT mice. Future studies using full-field ERGs will help to assess if moderate hypercapnia has a similar effect on global retinal responses.
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