Paradoxically, the photoreceptor cells in our retinas release more of their neurotransmitter, glutamate, in the dark, when there is nothing to see, than they do in the light. This is doubly surprising since although glutamate is a major signaling molecule in the retina and throughout the central nervous system, it is also a potent cytotoxin that, in large doses, can kill nearby cells.
What keeps our retinas from disintegrating each night as glutamate continues to be released is unknown, but growing evidence suggests our molecular protector may be zinc, a metal abundant in tissues throughout the body.
Zinc’s relationship to vision was first recognized when it was found that night blindness is associated with zinc deficiency, and recent studies have shown that a diet supplemented with this trace metal can reduce the progression of one form of age-related blindness. But despite its apparent benefits, not much is known about the relationship between zinc and the eye.
Richard Chappell, a professor of biological sciences at Hunter College, is at the MBL this summer with doctoral student Ivan Anastassov and Harris Ripps, a senior research scientist at MBL and emeritus professor of ophthalmology at the UIC College of Medicine in Chicago, to investigate how zinc may control the wily glutamate. Using the retina of the skate, a cartilaginous fish resembling a manta ray, they record electroretinograms (ERGs) to measure how retinal neurons respond to light stimuli in the presence and absence of normal levels of zinc.
Their preliminary results indicate that ionic zinc (Zn2+) is co-released with glutamate from skate rods, and feeds back onto the photoreceptor terminals to suppress the release of glutamate, thus providing an automatic gain control mechanism that reduces the risk of glutamate toxicity.
Demonstrating the role of Zn2+ in the regulation of glutamate release from skate rods is still a long way from fully understanding its potential use in therapy for human diseases where glutamate toxicity may be involved, but its ubiquity among vertebrates shows promise. The presence of available Zn2+ and/or its transporters has been observed in the photoreceptor region of salamanders, zebrafish, mice, and skates, but “The question is whether this is an integral part of the physiology of the retina,” says Ripps. “Once you understand the normal retina, you can determine the basis of retinal disorders.”
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