Ischaemic cell death has been implicated in a number of retinal diseases, including glaucomatous neuropathy, proliferative diabetic retinopathy and a range of vascular diseases. The cascade of events leading to cell death involves both cellular metabolic changes and a functional component. However, it is yet unknown how long these changes persist, whether all cell classes are affected, and the characteristics of recovery. Moreover, there have been few studies correlating the neurochemical changes with the ensuing functional changes. The aim of this thesis was to track the metabolic and functional recovery of the ischaemic rat retina, given the premise that: (1) amino acid neurochemistry reflects metabolic integrity and cellular identity, and; (2) the permeation of a cation channel probe called agmatine reflects channel functionality. Quantitative pattern recognition analysis of overlapping amino acid and agmatine expression profiles were used to provide a statistically robust classification of cells according to metabolic and functional characteristics. This classification was spatially complete and with single cell resolution. Finally, the electroretinogram was used to also assess retinal function and corroborate the observed neurochemical changes. These measures were taken at intervals for up to two weeks of reperfusion. The results show that by 48 hours of reperfusion, amino acid metabolism had returned to near normal levels, although cell classes were missing, and there was persistant cation channel gating anomalies. Immunocytochemical labeling identified a preferential loss of cone bipolar cells, with all remaining rod bipolar cells showing increased cation channel gating. The electroretinogram and agmatine experiments showed that this dysfunction is likely due to abnormal glutamate release from pre-synaptic photoreceptors, detected by changes in post-synaptic agmatine permeation, and not due to the presence of anomalous metabotropic glutamate receptors. Cholinergic amacrine cells demonstrated persistant neurochemical labeling, but did not show cationic flux following stimulation by glutamate agonists. In conclusion, the retina shows remarkable recovery in the amino acid metabolism, although functional changes persist. Finally, structural integrity or immunocytochemical labeling does not necessarily imply that cells maintain functional receptors, or that neurotransmitter release is normal secondary to disease. / Whole document restricted, but available by request, use the feedback form to request access.
| Identifer | oai:union.ndltd.org:ADTP/278618 |
| Date | January 2007 |
| Creators | Sun, Daniel |
| Publisher | ResearchSpace@Auckland |
| Source Sets | Australiasian Digital Theses Program |
| Language | English |
| Detected Language | English |
| Rights | Whole document restricted but available by request. Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated., http://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm, Copyright: The author |
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