The electrophysiological detection of subclinical abnormalities in asymptomatic members of Lebers hereditary optic neuropathy pedigrees.
Item
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Title
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The electrophysiological detection of subclinical abnormalities in asymptomatic members of Lebers hereditary optic neuropathy pedigrees.
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Identifier
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AAI3205024
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identifier
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3205024
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Creator
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Kleiner Hoffman, Lisa.
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Contributor
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Adviser: Louise Hainline
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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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Psychology, Experimental
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Abstract
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Background: Lebers Hereditary Optic Neuropathy (LHON) is a mitochondrial DNA (mtDNA) disorder where primarily male descendents are at greater risk for near or complete vision loss.;Purpose: Subclinical VEP abnormalities are hypothesized in normal asymptomatic LHON maternal relatives positive for the 11778 mtDNA mutation. Specifically, magnocellular and ON cells are hypothesized to express neurotoxic damage earlier in LHON. Firstly, larger cells, which are more metabolically active, may be more susceptible to compromises in oxidative phosphorylation and the derivative cycling effects of neurotoxicity. Secondly, the magnocellular pathway has been implicated in other disease states such as glaucoma, retinitis pigmentosa, Duchenne muscular dystrophy, and early-onset Alzheimers. The ON pathway has been implicated in other disease states as well, including nocturnal vision deficits, such as melanoma-associated retinopathy and congenital stationary night blindness.;Methods: Classic VEP stimuli and VEP stimuli aimed at probing ON/OFF and M/P specificity were employed. The first stimulus was a steady state spatial frequency (SF) sweep with horizontal square-wave grating patterns with contrast reversals at 7.5 Hz and a square-wave temporal signal. The second involved a conventional 32x32 contrast reversing checkerboard pattern (15 min checks), and contrast reversals at 1 Hz with a square wave temporal signal to evaluate transient VEP records. The third comprised checkerboard patterns where check size was swept and contrast reversals were modulated by a 1 Hz square wave temporal signal. The fourth employed a sweep through an array of isolated checks of increasing check size, where luminance was modulated sinusoidally in time, either above (positive contrast) or below (negative contrast) the luminance of the static background, producing appearing-disappearing bright or dark checks. The fifth employed a depth of modulation (DOM) sweep varying between 0% to 32% contrast across a 16x16 array of isolated checks in a similar appearance disappearance paradigm.;Results: Results indicated greater amplitude responses, vector mean amplitudes and signal-to-noise ratios in the asymptomatic LHON population as opposed to controls in both dominant and nondominant eyes, in both steady state and transient stimuli and in both the spatial and contrast domains. Significant responses, evaluated by means of a statistical application of magnitude-squared coherence (MSC) revealed greater coherence in the LHON population in the high frequency band correlated with P0, input to the cortex, which is consistent with an increased afferent signal in LHON. Intact and possibly enhanced magnocellular and parvocellular function was evidenced in the majority of LHON individuals. Analysis of an affected LHON individual and an anomalous asymptomatic participant with corroborative evidence of subsequent initial visual abnormalities indicated apparent magnocellular deficits.;Conclusion: Subclinical abnormalities are evidenced in asymptomatic LHON maternal relatives, consistent with a chronic progressive disorder of oxidative stress endemic to mtDNA mutations.
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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.
