Early retinal neuronal dysfunction in diabetic mice: Reduced light-evoked inhibition increases rod pathway signaling

Johnnie M. Moore-Dotson, Jamie J. Beckman, Reece E. Mazade, Mrinalini Hoon, Adam S. Bernstein, Melissa J. Romero-Aleshire, Heddwen L. Brooks, Erika D. Eggers

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Purpose: Recent studies suggest that the neural retinal response to light is compromised in diabetes. Electroretinogram studies suggest that the dim light retinal rod pathway is especially susceptible to diabetic damage. The purpose of this study was to determine whether diabetes alters rod pathway signaling. Methods: Diabetes was induced in C57BL/6J mice by three intraperitoneal injections of streptozotocin (STZ; 75 mg/kg), and confirmed by blood glucose levels > 200 mg/dL. Six weeks after the first injection, whole-cell voltage clamp recordings of spontaneous and light-evoked inhibitory postsynaptic currents from rod bipolar cells were made in dark-adapted retinal slices. Light-evoked excitatory currents from rod bipolar and AII amacrine cells, and spontaneous excitatory currents from AII amacrine cells were also measured. Receptor inputs were pharmacologically isolated. Immunohistochemistry was performed on whole mounted retinas. Results: Rod bipolar cells had reduced light-evoked inhibitory input from amacrine cells but no change in excitatory input from rod photoreceptors. Reduced light-evoked inhibition, mediated by both GABAA and GABAC receptors, increased rod bipolar cell output onto AII amacrine cells. Spontaneous release of GABA onto rod bipolar cells was increased, which may limit GABA availability for light-evoked release. These physiological changes occurred in the absence of retinal cell loss or changes in GABAA receptor expression levels. Conclusions: Our results indicate that early diabetes causes deficits in the rod pathway leading to decreased light-evoked rod bipolar cell inhibition and increased rod pathway output that provide a basis for the development of early diabetic visual deficits.

Original languageEnglish (US)
Pages (from-to)1418-1430
Number of pages13
JournalInvestigative Ophthalmology and Visual Science
Volume57
Issue number3
DOIs
StatePublished - Mar 1 2016

Keywords

  • Amacrine cells
  • Bipolar cells
  • Diabetes
  • GABA
  • Inhibition

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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