April 2014
Volume 55, Issue 13
ARVO Annual Meeting Abstract  |   April 2014
Retinal inhibitory signaling is compromised in diabetes
Author Affiliations & Notes
  • Johnnie Moore-Dotson
    Physiology, University of Arizona, Tucson, AZ
  • Reece Mazade
    Physiology, University of Arizona, Tucson, AZ
  • Adam Bernstein
    Physiology, University of Arizona, Tucson, AZ
    Biomedical Engineering, University of Arizona, Tucson, AZ
  • Melissa Romero-Aleshire
    Physiology, University of Arizona, Tucson, AZ
  • Heddwen Brooks
    Physiology, University of Arizona, Tucson, AZ
  • Erika Eggers
    Physiology, University of Arizona, Tucson, AZ
    Biomedical Engineering, University of Arizona, Tucson, AZ
  • Footnotes
    Commercial Relationships Johnnie Moore-Dotson, None; Reece Mazade, None; Adam Bernstein, None; Melissa Romero-Aleshire, None; Heddwen Brooks, None; Erika Eggers, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 1643. doi:
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      Johnnie Moore-Dotson, Reece Mazade, Adam Bernstein, Melissa Romero-Aleshire, Heddwen Brooks, Erika Eggers; Retinal inhibitory signaling is compromised in diabetes. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1643.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: Diabetic retinopathy causes severe retinal damage that ultimately leads to blindness. It was previously thought that diabetic retinal injury was solely a result of vascular damage, but recent studies have shown changes in retinal signaling that suggest altered inhibitory GABAergic signaling prior to vascular changes. We previously found that spontaneous GABAergic amacrine cell input to rod bipolar cells is increased without changes in morphology in early diabetes. The purpose of this study is to determine whether light-evoked inhibitory signaling in the inner retina is compromised in a mouse model of diabetes.

Methods: Diabetes was induced in C57BL/6J mice at 5 weeks of age by i.p. injections of streptozotocin (STZ) at a dose of 75 mg/kg over 3 days. Diabetes was confirmed by blood glucose levels >200 mg/dL. Six weeks post injections, whole-cell voltage clamp recordings of light-evoked (L) inhibitory (IPSCs) and excitatory postsynaptic currents (EPSCs) were made from rod bipolar cells (RBCs) in dark adapted retinal slices. RBCs were held at the reversal potential for cations or Cl- ions to isolate L-IPSCs or EPSCs, respectively. Light responses were elicited by a 30 ms full field LED stimulus. GABAA and GABAC receptor (R) inputs were pharmacologically isolated. The peak amplitude and charge transfer (Q) were measured.

Results: The L-EPSCs of RBCs that represent rod photoreceptor inputs were not different from control in STZ mice. The peak amplitude of L-IPSCs was significantly reduced in STZ mice (n = 17 cells) at multiple light intensities compared to control (n = 16 cells, p < 0.05). The Q from STZ mice was reduced at a rod dominant light intensity. The GABACR mediated response was on average reduced, but this was not significant. However, GABAAR mediated responses (p < 0.05) were attenuated at multiple intensities in STZ mice.

Conclusions: These results show that light-evoked inhibition to RBCs is decreased in early diabetes. The decrease in light-evoked inhibition of RBCs from STZ mice suggests that amacrine cells are less sensitive to light activation in diabetes. Reduced amacrine cell input is not due to decreased RBC activation because RBC L-EPSCs are not different in diabetic mice. These results are consistent with ERG data that indicates altered inhibitory signaling and likely contribute to the changes in retinal electrical signaling that occurs in diabetic retinopathy.

Keywords: 499 diabetic retinopathy • 498 diabetes • 688 retina  

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