Peroxidized docosahexaenoic acid causes RPE dysfunction: implications for retinal ageing and AMD

Bakker, Linda Margaretha 2008. Peroxidized docosahexaenoic acid causes RPE dysfunction: implications for retinal ageing and AMD. PhD Thesis, Cardiff University.

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Abstract

The aim of this study was to gain important insights into the effects of peroxidized docosahexaenoic acid (pDHA) on the retinal pigment epithelium (RPE), and whether its effects can cause RPE cell dysfunction in a way similar to that observed in retinal ageing and the pathogenesis of age-related macular degeneration (AMD). Initially, the time-course of in vitro peroxidation of DHA was monitored, culminating in formation of products able to absorb light above 400 nm. Cultured RPE cells were then exposed to this pDHA, which was shown to be toxic, both in dark and light-exposed conditions. Various cell viability assays were carried out indicating RPE cell death after exposure to pDHA is likely to occur by apoptosis. The effects of pDHA were reduced in the presence of various agents - a-tocopherol, glutathione, N-acetylcysteine, and phosphatidylethanolamine (PE). Measurements of singlet oxygen, transient and superoxide production were carried out to determine the photosensitizing properties of pDHA. The ability of PE to reduce the production of these species was investigated but it was shown to have no effect on their yield, although singlet oxygen lifetime was reduced. Finally, lysosomal enzyme activity, lysosomal integrity and accumulation of fluorescent and undegraded material were monitored after exposure to pDHA, demonstrating that pDHA was able to disrupt the ability of the RPE to fully degrade phagocytosed material. In summary, pDHA is able to affect RPE cell viability directly when exposed extracellularly, and can also affect essential normal functions of the RPE intracellularly. In conjunction with published findings that pDHA is present in the retina - both within and around the RPE - the data presented here support the theory that pDHA can play an important role in causing RPE dysfunction, resulting in a loss of the protective role these cells play for photoreceptors, as occurs in retinal ageing and AMD.

Item Type:	Thesis (PhD)
Status:	Unpublished
Schools:	Optometry and Vision Sciences
Subjects:	R Medicine > RE Ophthalmology
ISBN:	9781303213373
Date of First Compliant Deposit:	30 March 2016
Last Modified:	06 Nov 2024 15:12
URI:	https://orca.cardiff.ac.uk/id/eprint/54734

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