Dissertation/Thesis Abstract

Neuromodulatory and Cytoprotective Roles of Zinc in the Vertebrate Retina
by Anastassov, Ivan A., Ph.D., City University of New York, 2013, 149; 3553546
Abstract (Summary)

There is increasing evidence that the role of Zn2+ in the central nervous system is more complex and widespread than originally thought. Chelatable Zn2+ is co-localized with glutamate in the terminals of mossy fiber hippocampal and first order retinal neurons. The co-release of Zn2+ with glutamate in a stimulation-dependent manner has been shown in the hippocampus and the distal retina, while the electrophysiological effects of photoreceptor-released Zn2+ suggest a neuromodulatory role at the first visual synapse. This dissertation examines the neuromodulatory and cytoprotective roles of zinc in the vertebrate retina.

When endogenous Zn2+ release is chelated in a skate eyecup preparation, the photoreceptor-generated a-wave of the electroretinogram doubles. This treatment also depolarizes horizontal cells and enhances their light response, suggesting that in the absence of Zn2+, tonic release of glutamate from photoreceptors onto postsynaptic neurons is increased. Live cell imaging demonstrates that Zn2+ is released from photoreceptor terminals following Ca2+ entry through synaptic voltage-gated calcium channels. In isolated photoreceptors from salamander, chelation of extracellular Zn2+ significantly increases Ca2+ entry at the terminal and this effect is abolished when voltage-gated calcium channels are blocked pharmacologically.

In the skate, removal of retinal Zn2+ via intraocular injections of chelators severely damages the inner retina. In the absence of Zn2+, the retina develops classic signs of glutamate excitotoxicity; cell and tissue swelling, pyknosis and spongy appearance of the inner plexiform layer. Similar tissue characteristics are observed with injections of kainate, a well-known and potent excitotoxic agent. Additionally, neurons in the ganglion cell layer become necrotic with either kainate or chelator treatments, suggesting they are particularly sensitive to overactivation of glutamate receptors.

Taken together, these experiments show the importance of Zn2+ as a neuromodulatory agent at the first visual synapse, where control of glutamate release affects the transmission of the visual message and provides broad protection of the retina from excitotoxicity. Understanding the role of Zn2+ in the retina may provide novel insights into retinal diseases and contribute to our growing knowledge of zinc's important functions elsewhere in the CNS.

Indexing (document details)
Advisor: Chappell, Richard L.
Commitee: Banerjee, Probal, Goldfarb, Mitchell, Gordon, James, Seiple, William
School: City University of New York
Department: Biology
School Location: United States -- New York
Source: DAI-B 74/06(E), Dissertation Abstracts International
Source Type: DISSERTATION
Subjects: Biology, Neurosciences
Keywords: Calcium channels, Excitotoxicity, Glutamate, Modulation, Retina, Zinc
Publication Number: 3553546
ISBN: 9781267930330
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