Effects of a metabotropic glutamate 1 receptor antagonist on light responses of retinal ganglion cells in a rat model of retinitis pigmentosa.

Abstract

BACKGROUND:

Retinitis pigmentosa (RP) is a progressive retinal degenerative disease that causes deterioration of rod and cone photoreceptors. A well-studied animal model of RP is the transgenic P23H rat, which carries a mutation in the rhodopsin gene. Previously, I reported that blocking retinal GABAC receptors in the P23H rat increases light responsiveness of retinal ganglion cells (RGCs). Because activation of metabotropic glutamate 1 (mGlu1) receptors may enhance the release of GABA onto GABAC receptors, I examined the possibility that blocking retinal mGlu1 receptors might in itself increase light responsiveness of RGCs in the P23H rat.

METHODOLOGY/PRINCIPAL FINDINGS:

Electrical recordings were made from RGCs in isolated P23H rat retinas. Spike activity of RGCs was measured in response to brief flashes of light over a range of light intensities. Intensity-response curves were evaluated prior to and during bath application of the mGlu1 receptor antagonist JNJ16259685. I found that JNJ16259685 increased light sensitivity of all ON-center RGCs and most OFF-center RGCs studied. RGCs that were least sensitive to light showed the greatest JNJ16259685-induced increase in light sensitivity. On average, light sensitivity increased in ON-center RGCs by 0.58 log unit and in OFF-center RGCs by 0.13 log unit. JNJ16259685 increased the maximum peak response of ON-center RGCs by 7% but had no significant effect on the maximum peak response of OFF-center RGCs. The effects of JNJ16259685 on ON-center RGCs were occluded by a GABAC receptor antagonist.

CONCLUSIONS:

The results of this study indicate that blocking retinal mGlu1 receptors in a rodent model of human RP potentiates transmission of any, weak signals originating from photoreceptors. This augmentation of photoreceptor-mediated signals to RGCs occurs presumably through a reduction in GABAC-mediated inhibition.

• Authors: Ralph J Jensen
• Journal: PloS one (PLoS One) Vol. 8 Issue 10 Pg. e79126 ( 2013) ISSN: 1932-6203 [Electronic] United States
• PMID: 24205371 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• (3,4-dihydro-2H-pyrano(2,3)b-quinolin-7-yl)-(cis-4-methoxycyclohexyl) methanone
• Excitatory Amino Acid Antagonists
• Quinolines

Topics

• Animals
• Electrophysiology
• Excitatory Amino Acid Antagonists (pharmacology)
• Light Signal Transduction (drug effects)
• Photic Stimulation
• Quinolines (pharmacology)
• Rats, Transgenic
• Retinal Ganglion Cells (drug effects, radiation effects)
• Retinitis Pigmentosa (physiopathology)