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

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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Identifiers

ORCID for Savannah Lynn: orcid.org/0000-0003-2513-3144

ORCID for Eloise Keeling: orcid.org/0000-0003-0399-359X

ORCID for Andrew Lotery: orcid.org/0000-0001-5541-4305

ORCID for J. Arjuna Ratnayaka: orcid.org/0000-0002-1027-6938

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