title: Early Retinal Neuronal Dysfunction in Diabetic Mice: Reduced Light-Evoked Inhibition Increases Rod Pathway Signaling.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Physiology, University of Arizona, Tucson, Arizona, United States.
authors.forename: Johnnie M
authors.initials: JM
authors.lastname: Moore-Dotson
authors.affiliation: Graduate Interdisciplinary Program in Physiological Sciences, University of Arizona, Tucson, Arizona, United States.
authors.forename: Jamie J
authors.initials: JJ
authors.lastname: Beckman
authors.affiliation: Graduate Interdisciplinary Program in Physiological Sciences, University of Arizona, Tucson, Arizona, United States.
authors.forename: Reece E
authors.initials: RE
authors.lastname: Mazade
authors.affiliation: Department of Biological Structure, University of Washington, Seattle, Washington, United States.
authors.forename: Mrinalini
authors.initials: M
authors.lastname: Hoon
authors.affiliation: Department of Physiology, University of Arizona, Tucson, Arizona, United States.
authors.forename: Adam S
authors.initials: AS
authors.lastname: Bernstein
authors.affiliation: Department of Physiology, University of Arizona, Tucson, Arizona, United States.
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Romero-Aleshire
authors.affiliation: Department of Physiology, University of Arizona, Tucson, Arizona, United States.
authors.forename: Heddwen L
authors.initials: HL
authors.lastname: Brooks
authors.affiliation: Department of Physiology, University of Arizona, Tucson, Arizona, United States 4Department of Biomedical Engineering, University of Arizona, Tucson, Arizona, United States.
authors.forename: Erika D
authors.initials: ED
authors.lastname: Eggers
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000473:pathology / Q000503:physiopathology*; D003930:Diabetic Retinopathy / Q000473:pathology / Q000503:physiopathology*; D005074:Evoked Potentials, Visual / Q000502:physiology*; D005500:Follow-Up Studies; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018408:Patch-Clamp Techniques; D010775:Photic Stimulation; D055351:Retinal Neurons / Q000502:physiology*; D017948:Retinal Rod Photoreceptor Cells / Q000502:physiology*; D015398:Signal Transduction; D013997:Time Factors