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Rene Renteria, Nikolay Akimov, Songqing Lu; Diabetic retinopathy alters retinal ganglion cell function and light responsiveness in the Ins2Akita mouse model of diabetes. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2675. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Diabetic retinopathy (DR) causes vision loss, presumably when microvascular pathology damages neurons leading to cell loss. We have previously shown that retinal blood flow and a visual behavior are impaired in heterozygous male Ins2Akita mice, a model of Type 1 diabetes and early DR, but light responses of retinal ganglion cells (RGCs) have not been examined in diabetes. Here, we determined RGC functional parameters in diabetic Akita mice and non-diabetic littermates.
A multi-electrode array was used to record spiking from RGCs of Akita mice after 4-6 months of diabetes. Receptive fields (RFs) were mapped using Gaussian white-noise checkerboards (60 micron checks) presented at 25 Hz. The peak of the spike-triggered average (STA) stimulus checkerboard was fit with a 2D Gaussian to determine RF diameter (at 1 standard deviation). STA contrast was the amplitude of the temporal linear filter of the RF center. Surround strength was determined using an ellipsoid stimulus of increasing size fit to the RF. The intensity of a light square covering the array was varied sinusoidally at 18 contrasts ranging from 2.4% to 92% and presented at 3.75 Hz to find contrast threshold. Next, 10 temporal frequencies ranging from 0.75 Hz to 12.5 Hz were presented at 50% contrast to find optimal frequency and bandwidth. Whole-cell recordings of RGCs in whole-mounted retinas were used to determine intensity-response curves to 1 sec light steps over 6 logs of light intensity.
For both the ON and OFF RGC populations in diabetic Akita mice, more RGC RF centers were smaller and surrounds were slightly weaker compared to control animals. A significant proportion of diabetic ON and OFF RGCs also had weaker STA contrast. Contrast thresholds and optimal temporal frequencies, on the other hand, appeared unchanged by diabetes. Whole-cell light-evoked current and spiking data showed that ON and OFF RGCs from diabetic retinas were more sensitive than controls to stimuli at scotopic light intensities but became less responsive to increasing intensities of light stimuli into the photopic range, in both current and voltage clamp.
RGC function is altered in retinas of diabetic Akita mice. Because mice model early DR, without the problems of late proliferative DR, these results suggest that altered RGC function is an early pathology in DR.
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