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Rene C Renteria, Saurav Chandra, Nikolay Akimov, Eric Muir, Timothy Q. Duong, Divya Narayanan; Ocular Blood Flow Response Reduction and Electroretinogram Deficits during Hypercapnia in Diabetic Mice. Invest. Ophthalmol. Vis. Sci. 2016;57(12):612. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Ocular blood flow adjusts in response to metabolic challenges in healthy eyes, but the responses during diabetes are less well understood. We previously found that, in response to hypercapnic challenge, full-field electroretinogram (FF-ERG) responses are significantly compromised in diabetic Ins2Akita mice, a model of diabetic retinopathy (DR), but remain unaltered in wild-type (WT). Here, we begin to test our hypothesis that an inability to sufficiently alter blood flow under metabolic challenges in the diabetic mouse eye contributes to ERG deficits.
Choroidal and retinal blood flow (ChBF and RBF, respectively, determined using magnetic resonance imaging as we have previously described) and dark-adapted FF-ERG (intensity range: 0.0001 to 6.7 ScCds/m2, 4ms flash duration) were recorded from 8 C57Bl6J WT (aged 8.3±0.5 mos) and 6 Akita mice (aged 8.4±0.6 mos) under both regular room air and moderate hypercapnic challenge (5% CO2, 21% O2, balance N2). ERG amplitudes and implicit times (IT) for a-wave, b-wave, and oscillatory potentials (OPs) were measured, and 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 room air, Akita had lower ChBF (4.5±0.5 vs 6.3±0.5 in WT, p=0.02, ml/min/g) and RBF (0.8±0.1 vs 1.0±0.1 in WT, p=0.07) than WT. In response to hypercapnia, both WT and Akita showed significantly increased ChBF and RBF. However, for ChBF the percentage increase was significantly lower in Akita than in WT (13±2.3% in Akita vs 23 ±3.4% in WT, p=0.03) but not for RBF (9±1.1% in Akita vs 12±6.3% in WT, p=0.65). Akita b-waves and OPs have significantly reduced amplitudes and delayed ITs compared to WT. In response to hypercapnia, these responses showed further significant compromise in Akita but not in WT. No significant change was observed in a-wave responses or I1/2 in WT or Akita during room air or hypercapnic challenge. ChBF showed moderate correlation with b-wave fit amplitude (Vmax) in WT and in Akita under both conditions (r=0.65 to 0.68, p<0.05 for all comparisons), but RBF did not (all p>0.05).
When challenged with hypercapnia, an increase in ChBF and RBF occurred in both normal and diabetic mice. However, the ChBF increase in diabetic mice was significantly smaller than in normal mice, which may exacerbate neuronal dysfunction in DR.
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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