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Alpha (α)-crystallins as protectors in oxidative stress and photochemical damage of the retina

Trego, Melissa E. 2008. Alpha (α)-crystallins as protectors in oxidative stress and photochemical damage of the retina. PhD Thesis, Cardiff University.

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Abstract

Alpha (α)-crystallins (αA- and αB-) 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 αA-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 αA-crystallin yielded highly significant decreased cell viability, indicating a possible protection in the presence of αA-. To further investigate the in-vivo protective role of α-crystallins in the retina, in particular αA-. WT mice and αA-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, αA- 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 αB-crystallin expression in aA- K/O mice was not significantly upregulated at any time point. Therefore the absence of αA- may effect expression and potency of αB-crystallin in response to stress- related conditions. Results presented will demonstrate that the presence of α-crystallins, in particular, αA-, may play a protective role in oxidative stress to the RPE and photochemical damage of the retina.

Item Type: Thesis (PhD)
Status: Unpublished
Schools: Optometry and Vision Sciences
Subjects: R Medicine > RE Ophthalmology
ISBN: 9781303222238
Date of First Compliant Deposit: 30 March 2016
Last Modified: 19 Mar 2016 23:31
URI: http://orca-mwe.cf.ac.uk/id/eprint/55070

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