Blockade of Retinal Oscillations by Benzodiazepines Improves Efficiency of Electrical Stimulation in the Mouse Model of RP, rd10

Invest Ophthalmol Vis Sci. 2020 Nov 2;61(13):37. doi: 10.1167/iovs.61.13.37.

Abstract

Purpose: In RP, photoreceptors degenerate. Retinal prostheses are considered a suitable strategy to restore vision. In animal models of RP, a pathologic rhythmic activity seems to compromise the efficiency of retinal ganglion cell stimulation by an electrical prosthesis. We, therefore, strove to eliminate this pathologic activity.

Methods: Electrophysiologic recordings of local field potentials and spike activity of retinal ganglion cells were obtained in vitro from retinae of wild-type and rd10 mice using multielectrode arrays. Retinae were stimulated electrically.

Results: The efficiency of electrical stimulation was lower in rd10 retina than in wild-type retina and this was highly correlated with the presence of oscillations in retinal activity. Glycine and GABA, as well as the benzodiazepines diazepam, lorazepam, and flunitrazepam, abolished retinal oscillations and, most important, increased the efficiency of electrical stimulation to values similar to those in wild-type retina.

Conclusions: Treatment of patients with these benzodiazepines may offer a way to improve the performance of retinal implants in cases with poor implant proficiency. This study may open the way to a therapy that supports electrical stimulation by prostheses with pharmacologic treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Animals
  • Benzodiazepines / pharmacology
  • Disease Models, Animal*
  • Electric Stimulation Therapy*
  • Female
  • Glycine / pharmacology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Retina / physiopathology*
  • Retinal Ganglion Cells / drug effects*
  • Retinal Ganglion Cells / physiology
  • Retinitis Pigmentosa / physiopathology*
  • gamma-Aminobutyric Acid / pharmacology

Substances

  • Benzodiazepines
  • gamma-Aminobutyric Acid
  • Glycine