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.

Zinc Nutrition and Inflammation in the Aging Retina

“…Depolarization of the retinal neurons can induce zinc release at the plexiform layers, which provided the first evidence for the hypothesized neuro modulator role for zinc in the retina . Endogenous zinc is co‐released with glutamate from synaptic terminals of photoreceptors and, by negative feedback, reduces calcium entry and concomitant vesicular release of glutamate . This is, therefore, likely to protect the retina from glutamate excitotoxicity …”

“…Endogenous zinc is co‐released with glutamate from synaptic terminals of photoreceptors and, by negative feedback, reduces calcium entry and concomitant vesicular release of glutamate . This is, therefore, likely to protect the retina from glutamate excitotoxicity …”

“…[68,131,132] Endogenous zinc is co-released with glutamate from synaptic terminals of photoreceptors and, by negative feedback, reduces calcium entry and concomitant vesicular release of glutamate. [81,83] This is, therefore, likely to protect the retina from glutamate excitotoxicity. [83] Zinc can be released from the cellular compartments or stores by molecules such as MTs, by external stimuli.…”

“…[81,83] This is, therefore, likely to protect the retina from glutamate excitotoxicity. [83] Zinc can be released from the cellular compartments or stores by molecules such as MTs, by external stimuli. Amongst the many roles of zinc in intracellular processes, zinc release can lead to the activation and phosphorylation of the MAPK/ERK pathway [133] and/or zinc transporters.…”

“…[70][71][72] Inhibition of extracellular zinc on hemi-gap-junction channel currents on retinal horizontal cells in bass [73] Zinc release by depolarization of retinal cells in rat [74] Modulation of A-type potassium currents by zinc in retinal horizontal cells [75] Amacrine cells Differential modulation of signal from cones to horizontal cells by extracellular zinc [76] Zn(2+) modulates light responses of bipolar and amacrine cells in carp retina [77] Modulatory role of endogenous zinc upon glycinergic response in amacrine cells in rat retina [78] Suppression by zinc of transient OFF responses of carp amacrine cells on GABA receptors [79] Photoreceptors Synaptically released zinc from rod photoreceptors in zebrafish [80] Modulatory role of extracellular zinc upon calcium activity the photoreceptor terminal [81] Role of Yin Yang 1 in melatoninergic function of retinal photoreceptors. [82] Zinc co-release with glutamate by photoreceptors; cytoprotective role in skate retina [81,83] Translocation of zinc within photoreceptors in light stimulation [17] Stabilization of disc membranes in bovine and mice retina and in vitro model modelling [84][85][86][87][88] Role of KLF15 in repression of photoreceptor-specific gene expression in non-photoreceptor cells in vitro molecular model system [89] RPE Zinc decrease in RPE layer in disease in vitro [9] Regulatory role of melanin synthesis and melanosome formation in RPE cells in vitro and in vivo in rats [90][91][92] Protective role of zinc against oxidative stress in vitro RPE [32,93,94] Role of zinc in phagocytic and lysosomal activity in vitro RPE [95][96][97][98] Role of zinc in apoptosis in in vitro RPE…”