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Critical role of AGEs/ALEs in age-related dysfunction of the retinal pigment epithelium

Wu, Keqiang 2007. Critical role of AGEs/ALEs in age-related dysfunction of the retinal pigment epithelium. PhD Thesis, Cardiff University.

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Abstract

This study was to identify the critical role of advanced glycation and advanced lipoxidation end products in age-related RPE dysfunction in human eyes. Lipofuscin is an age pigment composed of incompletely degraded material derived from the photoreceptors and autophagy. With ageing, there is a gradual accumulation of lipofuscin pigment material in the lysosomal system within RPE that may have a direct influence on cell function. Evidences appeared that AGEs/ALEs might play an important role in the formation of age-related intracellular fluorescence in RPE cells including that associated with lipofuscin granules. Also, they might appreciably alter the expression and enzymatic activity in the RPE lysosomal system, causing disruption of lysosomal function and having severe implications for RPE health in the ageing eye. Our results showed there was a significant increase of auto-fluorescent granules accumulation in ARPE-19 cells after 28 days culture on glycated matrigel feeding with POS which means that AGEs/ALEs could increase lipofuscin accumulation within RPE in in vitro. These results were also confirmed by using primary RPE cells from 3 donors (male and female). Secondly, we also demonstrated that AGEs/ALEs accumulated within RPE could decrease Cathepsin D enzyme activities lead to cell dysfunction. Also Cathepsin B and APS activities were affected by AGEs/ALEs. Results also showed that the lysosomal enzyme activities were deficient by AGEs/ALEs through altered the gene expression of the enzymes in the RPE respectively. In summary, it has been demonstrated that the molecular and cellular function of the RPE could be transformed by non-enzymatic glycation.

Item Type: Thesis (PhD)
Status: Unpublished
Schools: Optometry and Vision Sciences
Subjects: R Medicine > RE Ophthalmology
ISBN: 9781303209505
Date of First Compliant Deposit: 30 March 2016
Last Modified: 12 Feb 2016 23:12
URI: http://orca-mwe.cf.ac.uk/id/eprint/54609

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