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Silke Becker, Rithwick Rajagopal, Bruce A Berkowitz, Frans Vinberg; Functional Analysis of Retinal Cells in Mouse Models of Type I and II Diabetes Using Ex Vivo Electroretinography. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3586. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Diabetic retinopathy (DR) is commonly thought of as a microvasculopathy. New data support a surprising hypothesis that the earliest evidence of a diabetes-induced lesion is photoreceptor dysfunction. Few studies have investigated the electroretinography (ERG) of both photoreceptors and downstream / supporting cell function. Here, we investigate this hypothesis using a new ex vivo ERG method in retinas from Type I and II diabetic mice.
Scotopic ex vivo ERG was recorded from isolated retinas, superfused with Ames’ medium (containing 6 mM glucose, 95%O2/5%CO2), from STZ-induced C57BL/6J or db/db (JAXTM #000642) diabetic mice, and their littermate non-diabetic controls (no STZ injection or db/wt). Mice with >250 mg/dL blood glucose level were considered diabetic. ON bipolar (Rb) and Müller glia (RM) cell responses were determined by subtracting ERG waveforms in the presence of DL-AP4 or Barium, respectively, from those in the absence of the pharmacological inhibitors. Photoreceptor responses (Rp) were recorded in the presence of both DL-AP4 and Barium.
Maximal photoreceptor response amplitude (Rp,max) was ~15% smaller at 3 and 6 months after the STZ-induced diabetes as compared to the controls. Rp,max was decreased by 30% in 6 mo. db/db mice. When plotted against the light stimulus intensity (I-Rb), the bipolar cell responses did not change at all in any of the diabetic mice. The Müller cell response amplitudes, RM, changed linearly with respect to the area under the photoreceptor responses. The linear relationship was changed by STZ-induced diabetes.
These data support early dysfunction of photoreceptors and Müller cells but not bipolar cells in both types of diabetes. Our data suggest that rod – bipolar cell signaling is not suppressed in the retinas extracted from the diabetic animals.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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