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Fundamental differences in patterns of retinal ageing between primates and mice

Research output: Contribution to journalArticle

Original languageEnglish
Article number12574 (2019)
Number of pages14
JournalScientific Reports
Volume9
DOIs
DateAccepted/In press - 6 Aug 2019
DatePublished (current) - 29 Aug 2019

Abstract

Photoreceptors have high metabolic demands and age rapidly, undermining visual function. We base our understanding mainly on ageing mice where elevated inflammation, extracellular deposition, including that of amyloid beta, and rod and cone photoreceptor loss occur, but cones are not lost in ageing primate although their function declines, revealing that primate and mouse age differently. We examine ageing primate retinae and show elevated stress but low inflammation. However, aged primates have a >70% reduction in adenosine triphosphate (ATP) and a decrease in cytochrome c oxidase. There is a shift in cone mitochondrial positioning and glycolytic activity increases. Bruch’s membrane thickens but unlike in mice, amyloid beta is absent. Hence, reduced ATP may explain cone functional decline in ageing but their retained presence offers the possibility of functional restoration if they can be fuelled appropriately to restore cellular function. This is important because as humans we largely depend on cone function to see and are rarely fully dark adapted. Presence of limited aged inflammation and amyloid beta deposition question some of the therapeutic approaches taken to resolve problems of retinal ageing in humans and the possible lack of success in clinical trials in macular degeneration that have targeted inflammatory agents.

    Research areas

  • Experimental models of disease, Retina

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    Rights statement: This is the final published version of the article (version of record). It first appeared online via Springer Nature at https://www.nature.com/articles/s41598-019-49121-0. Please refer to any applicable terms of use of the publisher.

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