Richard L. Chappell

This review covers a broad range of topics related to the actions of zinc on the cells of the vertebrate retina. Much of this review relies on studies in which zinc was applied exogenously, and therefore the results, albeit highly suggestive, lack physiologic significance. This view stems from the fact that the concentrations of zinc used in these studies may not be encountered under the normal circumstances of life. This caveat is due to the lack of a zinc-specific probe with which to measure the concentrations of Zn2+ that may be released from neurons or act upon them. However, a great deal of relevant information has been garnered from studies in which Zn2+ was chelated, and the effects of its removal compared with findings obtained in its presence. For a more complete discussion of the consequences of depletion or excess in the body’s trace elements, the reader is referred to a recent review by Ugarte et al. in which they provide a detailed account of the interactions, toxicity, and metabolic activity of the essential trace elements iron, zinc, and copper in retinal physiology and disease. In addition, Smart et al. have published a splendid review on the modulation by zinc of inhibitory and excitatory amino acid receptor ion channels.

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.

Labeling for zinc transporter protein-3 (ZnT-3), which can be found localized to glutamatergic vesicles elsewhere in the nervous system, has revealed an un

Photographic images of the optokinetic response (OKR) of larval zebrafish permitted the calculation of the amplitude and velocity of the response to gratings of various spatial frequencies rotating at different speeds. At low spatial frequencies, the amplitude of the OKR did not vary significantly for drum speeds ranging from 24 to 108 degrees/sec. Plotting the velocity of the OKR as a function of drum speed gave rise to a bell-shaped curve, with a maximum at about 48 degrees/sec. Interestingly, both eyes exhibited an asymmetric response to the rotating drum, that is, they were more responsive to temporal-to-nasal rotation than to nasal-to-temporal motion. Although this asymmetry persisted over the entire range of drum speeds tested, the situation was reversed when tested with gratings of higher spatial frequency (i.e., the eyes became more responsive to rotation in the nasal-to-temporal direction). The amplitude of the OKR for both eyes exhibited an inverse relation to increasing spatial frequency of the stimulus, whereas the velocity of the OKR showed a steep decline within the range of 0.08 to 0.14 cycles/degree. The data indicate that zebrafish are more responsive to objects with low spatial frequencies moving from behind the animal's head toward the frontal plane, and to high spatial frequencies of objects moving across the frontal plane (perpendicular to the anterior-posterior axis of the eye).