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Michael Flood, Erika D Eggers; Light adaptation is impaired at the ganglion cell level after six weeks of diabetes. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5857.
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© ARVO (1962-2015); The Authors (2016-present)
There is growing evidence to suggest that normal retinal signaling is disrupted early on in diabetes, long before the onset of diabetic retinopathy. Previously, we have shown that after six weeks of diabetes in a mouse model, inhibitory inputs to rod bipolar cells are significantly reduced. The purpose of this study was to determine whether these upstream changes have a significant impact on ganglion cell signaling.
Diabetes was induced in C57BL/6J mice at 5 weeks of age by three consecutive i.p. [E1] injections of streptozotocin (STZ, 75 mg/kg). Diabetes was confirmed by blood glucose levels > 200 mg/dL. Six weeks post injections, whole-cell voltage clamp recordings of light-evoked (L) and spontaneous (s) excitatory post synaptic currents (EPSCs) were made from ON ganglion cells by holding at -60 mV, the reversal potential for chloride ions. µM). Light responses were elicited at multiple intensities by a 30ms full field LED stimulus (λ = 525 nm). Light adaptation was performed by exposing retinal slices to a 5 minute rod-saturating background, which was subsequently maintained. Light adapted responses were normalized on a cell to cell basis to the dark adapted response at the highest recorded intensity. All experiments were performed under infrared illumination to preserve retinal sensitivity. The peak and charge transfer (Q) were measured for all evoked responses. A rough measure of spontaneous activity for each cell was made by calculating the Q during the second preceding each light response and averaging for each condition. All light response data was analyzed by 2-way repeated measures ANOVA. sEPSC data was analyzed by paired t-tests. For these preliminary results, diabetic animals were compared directly to wild type ones.
No significant differences were found in the peak amplitude or charge transfer of raw L-EPSCs between wild type (n=7) and diabetic (n=9) animals. The total amount (Q) of spontaneous activity in diabetic animals was higher on average than in wild type, but this trend was not significant. For the light adapted responses, no significant differences in peak amplitude were found, but charge transfer was significantly larger for diabetic animals at 95000 and 950000 photons/um2/s.
After 6 weeks of diabetes, the overall sensitivity of ON ganglion cells is not significantly affected, but their ability to adapt to increased light levels may be compromised.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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