April 2011
Volume 52, Issue 14
ARVO Annual Meeting Abstract  |   April 2011
Lowering Electrical Stimulation Thresholds of Retinal Ganglion Cells in Degenerate Retina Pharmacologically
Author Affiliations & Notes
  • Ralph J. Jensen
    Ctr Innovative Vis Rehab, Boston VA Med Ctr, Boston, Massachusetts
  • Joseph F. Rizzo, III
    Ctr Innovative Vis Rehab, Boston VA Med Ctr, Boston, Massachusetts
    Mass Eye & Ear Infirmary, Harvard University, Boston, Massachusetts
  • Footnotes
    Commercial Relationships  Ralph J. Jensen, None; Joseph F. Rizzo, III, None
  • Footnotes
    Support  Rehabilitation R & D Service, Department of Veterans Affairs
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 4973. doi:
  • Views
  • Share
  • Tools
    • Alerts
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Ralph J. Jensen, Joseph F. Rizzo, III; Lowering Electrical Stimulation Thresholds of Retinal Ganglion Cells in Degenerate Retina Pharmacologically. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4973.

      Download citation file:

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

  • Supplements

Purpose: : This work is related to the efforts of the Boston Retinal Implant Project to develop a subretinal prosthesis to restore vision to the blind. Clinical studies have shown that much more current is needed to evoke a light percept (phosphene) in subjects with retinitis pigmentosa than in normal, healthy subjects. The specific purpose of this study was to investigate whether the amount of current needed to activate retinal ganglion cells (RGCs) in an animal model of retinitis pigmentosa can be lowered pharmacologically.

Methods: : We sought to reduce stimulation thresholds of P23H-line 1 rat RGCs by blocking GABA receptor mediated inhibition in the retina. Specifically, we examined the effects of TPMPA (GABA-C receptor antagonist) and SR95531 (GABA-A receptor antagonist) on the electrically evoked responses of RGCs to biphasic current pulses delivered to the subretinal surface through a 400-µm diameter electrode. The experiments were conducted in vitro on the isolated retina.

Results: : Light-evoked responses were obtained from all P23H-line 1 rats (n = 18; 6-10 months of age). Both TPMPA and SR95531 reduced the stimulation thresholds of ON-center RGCs on average by 15% and 20% respectively. Co-application of the two GABA receptor antagonists had the greatest effect, on average reducing stimulation thresholds by 32%. In addition, co-application of the two GABA receptor antagonists increased the magnitude of the electrically evoked responses on average 3.0-fold. For OFF-center RGCs, TPMPA had little or no effect on stimulation thresholds, and SR95531 (applied alone or in combination with TPMPA) had variable effects on stimulation thresholds.

Conclusions: : GABA receptor antagonists lower stimulation thresholds of ON-center RGCs. It is proposed that the lowered thresholds are due to a blockade of GABA receptors on the axon terminals of ON bipolar cells, thereby increasing electrically evoked release of the excitatory neurotransmitter glutamate from these cells.

Keywords: retina • ganglion cells • electrophysiology: non-clinical 

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.