Confocal microscopy of diabetic lens cataractogenesis

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dc.contributor.advisor Kistler, Joerg en
dc.contributor.advisor Green, Colin en
dc.contributor.author Bond, Jacqueline en
dc.date.accessioned 2007-07-11T02:13:24Z en
dc.date.available 2007-07-11T02:13:24Z en
dc.date.issued 1998 en
dc.identifier THESIS 98-250 en
dc.identifier.citation Thesis (PhD--Biological Sciences)--University of Auckland, 1998 en
dc.identifier.uri http://hdl.handle.net/2292/862 en
dc.description Full text is available to authenticated members of The University of Auckland only. en
dc.description.abstract Diabetic individuals have a greatly increased risk of forming lens cataract. Experimentally induced Diabetic and galactosaemic cataract in rats have been used extensively as models to determine the Molecular and cellular mechanisms underlying diabetic lens opacification. In both models, discrete Opacities form early in cataractogenesis as a result of fluid accumulation and tissue breakdown in the lens cortex. Previous images of lens cellular changes during cataract formation, produced controversial results regarding the process of tissue liquefaction. Electron microscopy showed fields of few cells; alternatively, light micrographs showed larger fields but with lower resolution. These methods do not allow for the adequate sampling and resolution of cells in the liquefaction zone. I have re-addressed this issue using the confocal laser scanning microscope in combination with specific membrane labels. My results showed the appearance of initially only a few swollen cells about 200tr1mfr om the Equatorial periphery, and subsequently the massive cellular breakdown and tissue liquefaction inthis region. This localised phenomenon appeared incompatible with open gap junction channels and one could hypothesise that they closed early in diabetic cataractogenesis. Electrophysiological measurements, however, did not show a sudden drop of membrane potential around the liquefaction zone as could have been expected if channels closed to a large extent. Instead, I observed a more global depolarisation of lens tissue. The verification of these electrophysiological results with the microinjection and passage of the gap junction permeable tracer Neurobiotin failed because the delivery of tracer through the microelectrodes was insufficient for the visualisation with the confocal microscope. Better results were obtained with a newly developed "bulk loading" method. Neurobiotin loading highlighted damaged cells long before swollen cells and liquefactionbecame evident. It also showed that these damaged cells partially uncoupled from their neighbours, as tracer movement was restricted. Most normal appearing cells, however, received small quantities of the tracer molecule, hence, remained coupled at least to a limited extent. Electrophysiological and tracer experiments thus support a model whereby elevated sugar induces an increased leakiness of membranes to the extracellular space, and restricted cell-cell communication. It is hypothesised that these phenomena disrupt normal fluid circulation in the lens, resulting in fluid accumulation, cells welling, and eventually membrane rupture. en
dc.language.iso en en
dc.publisher ResearchSpace@Auckland en
dc.relation.ispartof PhD Thesis - University of Auckland en
dc.relation.isreferencedby UoA9984066814002091 en
dc.rights Restricted Item. Available to authenticated members of The University of Auckland. en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. en
dc.rights.uri https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm en
dc.title Confocal microscopy of diabetic lens cataractogenesis en
dc.type Thesis en
thesis.degree.discipline Biological Sciences en
thesis.degree.grantor The University of Auckland en
thesis.degree.level Doctoral en
thesis.degree.name PhD en
dc.rights.holder Copyright: The author en


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