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Significance of Potassium Homeostasis for Neurodegeneration in Glaucoma

dc.creatorFischer, Rachel Anne
dc.date.accessioned2020-08-22T20:56:38Z
dc.date.available2019-09-05
dc.date.issued2019-09-05
dc.identifier.urihttps://etd.library.vanderbilt.edu/etd-09042019-184152
dc.identifier.urihttp://hdl.handle.net/1803/14080
dc.description.abstractVision loss during glaucoma results from degeneration of retinal ganglion cell (RGC) axons. Glaucoma produces deficits in axon transport in RGCs prior to structural degeneration, representing a potential therapeutic window to interrupt axonopathy and prevent irreversible vision loss. Furthermore, studies indicate that axon transport deficits are accompanied by electrophysiological impairment. Electrophysiological studies in the Microbead Occlusion Model of murine glaucoma reveal that RGCs with deficits in axon transport have a reduced ability to maintain spiking frequency that arises from impaired membrane repolarization. This repolarization phenotype arises from reduced cation flux and K+ dyshomeostasis that accompanies pressure-induced decreases in Na/K-ATPase expression and activity. In vitro studies with purified RGCs indicate that elevated pressure induces early internalization of Na/K-ATPase that, when reversed, stabilizes cation flux and prevents K+ dyshomeostasis. Furthermore, pharmacological inhibition of the Na/K-ATPase is sufficient to replicate pressure-induced cation influx and repolarization phase phenotypes in healthy RGCs. Our findings identify a failure to maintain electrochemical gradients and cation dyshomeostasis as an early phenotype of glaucomatous pathology in RGCs.
dc.format.mimetypeapplication/pdf
dc.subjectRetina
dc.subjectNa/K-ATPase
dc.subjectGlaucoma
dc.titleSignificance of Potassium Homeostasis for Neurodegeneration in Glaucoma
dc.typedissertation
dc.contributor.committeeMemberYaqiong Xu
dc.contributor.committeeMemberCharles D. Weaver
dc.contributor.committeeMemberDavid J. Calkins
dc.contributor.committeeMemberRebecca M. Sappington
dc.type.materialtext
thesis.degree.namePHD
thesis.degree.leveldissertation
thesis.degree.disciplinePharmacology
thesis.degree.grantorVanderbilt University
local.embargo.terms2019-09-05
local.embargo.lift2019-09-05
dc.contributor.committeeChairJerod S. Denton


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