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The complexities underlying age-related macular degeneration- could Amyloid beta play an important role?

The complexities underlying age-related macular degeneration- could Amyloid beta play an important role?
The complexities underlying age-related macular degeneration- could Amyloid beta play an important role?
Age-related Macular Degeneration (AMD) causes irreversible loss of central vision for which there is no effective treatment. Incipient pathology is thought to occur in the retina for many years before AMD manifests from midlife onwards to affect a large proportion of the elderly. Although genetic as well as non-genetic/environmental risks are recognised, its complex aetiology makes it difficult to identify susceptibility, or indeed what type of AMD develops or how quickly it progresses in different individuals. Here we summarise the literature describing how the Alzheimer’s-linked Amyloid beta (A) group of misfolding proteins accumulate in the retina. The discovery of this key driver of Alzheimer’s disease in the senescent retina was unexpected and surprising, enabling an altogether different perspective of AMD. We argue that A fundamentally differs from other substances which accumulate in the ageing retina, and discuss our latest findings from a mouse model in which physiological amounts of A were subretinally-injected to recapitulate salient features of early AMD within a short period. Our discoveries as well as those of others suggest the pattern of A accumulation and pathology in donor aged/AMD tissues are closely reproduced in mice, including late-stage AMD phenotypes, which makes them highly attractive to study dynamic aspects of A-mediated retinopathy. Furthermore, we discuss our findings revealing how A behaves at single-cell resolution, and consider the long-term implications for neuroretinal function. We propose A as a key element in switching to a diseased retinal phenotype, which is now being used as a biomarker for late-stage AMD.
amyloid beta-protein, age-related macular degeneration, retinal neurons
1673-5374
538-548
Lynn, Savannah
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Keeling, Eloise
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Munday, Rosie
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Gabha, Gagandeep
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Griffiths, Helen
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Lotery, Andrew
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Ratnayaka, J. Arjuna
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Lynn, Savannah
de0c4ec2-8a3c-4b16-9e47-ea13abc32a3b
Keeling, Eloise
abc30700-b1ed-49ed-ba1c-078856e01b7c
Munday, Rosie
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Gabha, Gagandeep
afa03bf5-df62-4868-8228-bd87a235363e
Griffiths, Helen
a097fdaa-d3d6-49a9-9c69-0e6e5a5d518b
Lotery, Andrew
5ecc2d2d-d0b4-468f-ad2c-df7156f8e514
Ratnayaka, J. Arjuna
002499b8-1a9f-45b6-9539-5ac145799dfd

Lynn, Savannah, Keeling, Eloise, Munday, Rosie, Gabha, Gagandeep, Griffiths, Helen, Lotery, Andrew and Ratnayaka, J. Arjuna (2017) The complexities underlying age-related macular degeneration- could Amyloid beta play an important role? Neural Regeneration Research, 12 (4), 538-548. (doi:10.4103/1673-5374.205083).

Record type: Article

Abstract

Age-related Macular Degeneration (AMD) causes irreversible loss of central vision for which there is no effective treatment. Incipient pathology is thought to occur in the retina for many years before AMD manifests from midlife onwards to affect a large proportion of the elderly. Although genetic as well as non-genetic/environmental risks are recognised, its complex aetiology makes it difficult to identify susceptibility, or indeed what type of AMD develops or how quickly it progresses in different individuals. Here we summarise the literature describing how the Alzheimer’s-linked Amyloid beta (A) group of misfolding proteins accumulate in the retina. The discovery of this key driver of Alzheimer’s disease in the senescent retina was unexpected and surprising, enabling an altogether different perspective of AMD. We argue that A fundamentally differs from other substances which accumulate in the ageing retina, and discuss our latest findings from a mouse model in which physiological amounts of A were subretinally-injected to recapitulate salient features of early AMD within a short period. Our discoveries as well as those of others suggest the pattern of A accumulation and pathology in donor aged/AMD tissues are closely reproduced in mice, including late-stage AMD phenotypes, which makes them highly attractive to study dynamic aspects of A-mediated retinopathy. Furthermore, we discuss our findings revealing how A behaves at single-cell resolution, and consider the long-term implications for neuroretinal function. We propose A as a key element in switching to a diseased retinal phenotype, which is now being used as a biomarker for late-stage AMD.

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Ratnayaka et al_Manuscript - Accepted Manuscript
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Accepted/In Press date: 19 March 2017
e-pub ahead of print date: 4 May 2017
Keywords: amyloid beta-protein, age-related macular degeneration, retinal neurons

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Local EPrints ID: 412411
URI: https://eprints.soton.ac.uk/id/eprint/412411
ISSN: 1673-5374
PURE UUID: fd9946bc-2d03-420b-bc8b-a3a5ac4303cb
ORCID for Savannah Lynn: ORCID iD orcid.org/0000-0003-2513-3144
ORCID for Andrew Lotery: ORCID iD orcid.org/0000-0001-5541-4305
ORCID for J. Arjuna Ratnayaka: ORCID iD orcid.org/0000-0002-1027-6938

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Date deposited: 17 Jul 2017 13:41
Last modified: 26 Nov 2019 01:48

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Contributors

Author: Savannah Lynn ORCID iD
Author: Eloise Keeling
Author: Rosie Munday
Author: Gagandeep Gabha
Author: Helen Griffiths
Author: Andrew Lotery ORCID iD

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