Faculty Collaboration Database

Effects of kynurenate and other excitatory amino acid antagonists as blockers of light- and kainate-induced retinal rod photoreceptor disc shedding. J Comp Neurol 1988 Aug 08;274(2):295-303

Date

08/08/1988

Pubmed ID

3264839

DOI

10.1002/cne.902740212

Scopus ID

2-s2.0-0023720873 (requires institutional sign-in at Scopus site)   11 Citations

Abstract

Photoreceptor disc shedding in the retina involves detachment of discs from distal outer segments and phagocytosis of those discs by adjacent pigment epithelial cells. The disc-shedding process balances the continuous renewal of photosensitive membrane. In amphibians, rod disc shedding normally is light-stimulated. However, excitatory amino acids such as kainate stimulate disc shedding independent of a dark-light transition. Excitatory amino acid-induced disc shedding is accompanied by toxic changes within the retina. To evaluate the possible role of an endogenous excitatory amino acid in the regulation of light-evoked disc shedding, we examined the effects of excitatory amino acid antagonists on kainate-induced and light-evoked disc shedding and on retinal toxicity. Using eyecups from Rana pipiens, we found that kynurenate, D-O-phosphoserine, and cis-2,3-piperidine dicarboxylic acid (cis-PDA) all block both the neurotoxic and disc-shedding effects of kainate. Kynurenate and D-O-phosphoserine, but not cis-PDA, also block light-evoked disc shedding. Our analysis suggests that kynurenate blocks the mechanism by which light "triggers" disc shedding rather than directly inhibiting disc detachment and phagocytosis. The observation that cis-PDA antagonizes the effects of kainate, but not light, suggests that the receptor mediating the kainate effect on disc shedding may not be involved in the normal initiation of the response by light. In contrast, our data on kynurenate suggest that it antagonizes an endogenous mechanism involved in the normal control of disc shedding. Thus, analysis of the differences between cis-PDA and kynurenate as antagonists in the retina may yield important insight into the mechanism by which light initiates disc shedding.

Author List

Besharse JC, Spratt G, Reif-Lehrer L

Author

Joseph C. Besharse PhD, MA Emeritus Professor in the Cell Biology Neurobiology and Anatomy department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
In Vitro Techniques
Kainic Acid
Kynurenic Acid
Light
Neurotoxins
Ouabain
Phosphoserine
Photoreceptor Cells
Pipecolic Acids
Rana pipiens
Reference Values