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Title: Alpha (alpha)-crystallins as protectors in oxidative stress and photochemical damage of the retina
Author: Trego, Melissa E.
ISNI:       0000 0004 2746 768X
Awarding Body: Cardiff University
Current Institution: Cardiff University
Date of Award: 2008
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Alpha (α)-crystallins (aA- and cxB-) once thought to be exclusive to the lens, have been discovered in the sensory retina and may act as molecular chaperones against cellular stresses. The premise of this work examined the potential protective role of α-crystallins in both the retinal pigment epithelium (RPE) and retina in-vitro and in-vivo respectively during oxidative stress or photochemical damage. Initial in-vitro work compared growth characteristics of wild-type (WT) and α-crystallin knock-out (K/O) mice RPE to their human counterparts revealing strong similarities. Mitochondrial viability of all cell types treated with hydrogen peroxide (H2O2) or 7-butyhydroperoxide (BOOH) for 24hrs revealed that RPE lacking α-crystallin yielded highly significant decreased cell viability, indicating a possible protection in the presence of α. To further investigate the in-vivo protective role of α-crystallins in the retina, in particular aA-. WT mice and aA-crystallin K/O mice were exposed to moderate levels of continuous blue light daily up to 7 days. Visual function was assessed with electroretinography (ERG) on all animals before exposure, immediately after exposure, and after a 10 day recovery period. Retinal morphology was examined immediately after and after a 10 day recovery period from light exposure. Although both strains revealed continual decline in their visual function with little morphological changes, aA- K/O mice degenerated significantly faster during their 10 day recovery period, both functionally and morphologically. Protein analysis revealed that WT mice exhibited statistically significant upregulation of the α-crystallins during their recovery period, while aB-crystallin expression in aA- K/O mice was not significantly upregulated at any time point. Therefore the absence of aA- may effect expression and potency of aB-crystallin in response to stress- related conditions. Results presented will demonstrate that the presence of α-crystallins, in particular, aA-, may play a protective role in oxidative stress to the RPE and photochemical damage of the retina.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available