title: Cytoprotection by endogenous zinc in the vertebrate retina.
abstract: Our recent studies have shown that endogenous zinc, co-released with glutamate from the synaptic terminals of vertebrate retinal photoreceptors, provides a feedback mechanism that reduces calcium entry and the concomitant vesicular release of glutamate. We hypothesized that zinc feedback may serve to protect the retina from glutamate excitotoxicity, and conducted in vivo experiments on the retina of the skate (Raja erinacea) to determine the effects of removing endogenous zinc by chelation. These studies showed that removal of zinc by injecting the zinc chelator histidine results in inner retinal damage similar to that induced by the glutamate receptor agonist kainic acid. In contrast, when an equimolar quantity of zinc followed the injection of histidine, the retinal cells were unaffected. Our results are a good indication that zinc, co-released with glutamate by photoreceptors, provides an auto-feedback system that plays an important cytoprotective role in the retina.
authors.affiliation: Department of Biological Sciences, Hunter College and the Graduate Center, CUNY, New York, New York, USA; Marine Biological Laboratory, Woods Hole, Massachusetts, USA.
authors.forename: Ivan
authors.initials: I
authors.lastname: Anastassov
authors.forename: Harris
authors.initials: H
authors.lastname: Ripps
authors.forename: Richard L
authors.initials: RL
authors.lastname: Chappell
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology*; D002614:Chelating Agents / Q000494:pharmacology; D003623:Dark Adaptation / Q000187:drug effects / Q000502:physiology; D003627:Data Interpretation, Statistical; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005123:Eye / Q000166:cytology; D018698:Glutamic Acid / Q000378:metabolism; D006639:Histidine / Q000633:toxicity; D007608:Kainic Acid / Q000494:pharmacology; D009336:Necrosis; D020419:Photoreceptor Cells, Vertebrate / Q000502:physiology; D012160:Retina / Q000187:drug effects / Q000502:physiology*; D012860:Skates, Fish / Q000502:physiology*; D015032:Zinc / Q000378:metabolism / Q000502:physiology*
chemical_list: D002614:Chelating Agents; D018690:Excitatory Amino Acid Agonists; D018698:Glutamic Acid; D006639:Histidine; D015032:Zinc; D007608:Kainic Acid
keywords: chelation; cytoprotection; glutamate excitotoxicity; ionic zinc; retinal histology