Localization and physiology of zinc in the vertebrate retina.
Item
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Title
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Localization and physiology of zinc in the vertebrate retina.
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Identifier
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AAI3213158
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identifier
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3213158
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Creator
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Redenti, Stephen M.
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Contributor
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Adviser: Richard L. Chappell
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Date
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2006
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Language
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English
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Publisher
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City University of New York.
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Subject
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Biology, Neuroscience
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Abstract
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A growing body of evidence indicates that zinc is essential for signaling and survival of neurons in the central nervous system. In the retina endogenous zinc modulates a number of cell and receptor subtypes. The focus of this dissertation is to examine the zinc content in living retinal tissue and measure its neuromodulatory effects. Results show the presence of zinc in all retinal layers and indicate a general downmodulation of synaptic transmission at the level of the outer plexiform layer. Evidence suggests a pool of zinc associated with synaptic vesicles in photoreceptor terminals. By removing zinc released into the synapse between photoreceptors, horizontal, and bipolar cells, whole cell patched horizontal cell inward currents were significantly enhanced. With synaptic zinc removed in situ, increased amplitudes in the b-wave of the electroretinogram (ERG) were recorded in both pure-rod and duplex retina and shifts in sensitivity observed. Zinc concentration in synaptic vesicles is regulated by zinc transporter-3 (ZnT-3) of the SLC30 family of transporters. Retinal slices incubated with antibodies directed against the ZnT-3 protein showed localization in the regions of the inner segments, outer nuclear, and ganglion cell layers. Examination of isolated retinal cell ZnT-3 localization revealed consistent reactivity of glial Mueller cell soma and endfeet. This finding suggests that ZnT-3 may be involved in zinc transport via Mueller cells in addition to its established role in vesicular membranes. When intracellular retinal zinc was imaged using a membrane-permeant fluorescent zinc probe, results showed high concentrations in photoreceptor outer segments with lower levels in ganglion and plexiform layers. For intracellular zinc to function as a retinal neuromodulator, synaptic release would be necessary. By depolarizing retinal slices, in the presence of a membrane-impermeant fluorescent zinc probe, release of synaptic zinc was visualized in the region of phototoreceptor outer segments and the outer plexiform layer. Over time, increased extracellular zinc was visualized spreading across all retinal layers.;Zinc homeostasis is essential to retinal function from transcription factor activation to cell surface receptor modulation. Imbalances in retinal zinc levels contribute to Age-Related Macular Degeneration, night blindness, ocular immune suppression and apoptosis. Greater understanding of retinal zinc activity will be essential for delineating mechanisms of neural processing in health and disease.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
