The best magazine
Abstract and Introduction
Abstract
Age-related macular degeneration (AMD) is one of the most common causes of irreversible blindness affecting nearly 50 million individuals globally. The disease is characterised by progressive loss of central vision, which has significant implications for quality of life concerns in an increasingly ageing population. AMD pathology manifests in the macula, a specialised region of the retina, which is responsible for central vision and perception of fine details. The underlying pathology of this complex degenerative disease is incompletely understood but includes both genetic as well as epigenetic risk factors. The recent discovery that amyloid beta (Aβ), a highly toxic and aggregate-prone family of peptides, is elevated in the ageing retina and is associated with AMD has opened up new perspectives on the aetiology of this debilitating blinding disease. Multiple studies now link Aβ with key stages of AMD progression, which is both exciting and potentially insightful, as this identifies a well-established toxic agent that aggressively targets cells in degenerative brains. Here, we review the most recent findings supporting the hypothesis that Aβ may be a key factor in AMD pathology. We describe how multiple Aβ reservoirs, now reported in the ageing eye, may target the cellular physiology of the retina as well as associated layers, and propose a mechanistic pathway of Aβ-mediated degenerative change leading to AMD.
Introduction
Age-related macular degeneration (AMD) is a complex ocular disorder affecting a critical region of the retina known as the macula, which is crucial for central vision and perception of fine detail. The disease is the primary cause of irreversible blindness in societies with demographics favouring increasing age. The aetiology of this degenerative disorder is poorly understood, but contains both genetic as well as environmental risk factors. Central to degenerative pathology is the loss of visual function, which is associated with atrophy of photoreceptors and the underlying retinal pigment epithelium (RPE) that forms the blood–retinal barrier. Retinal ganglion cells (RGC) and the RPE monolayer were recently identified as a major source of amyloid beta (Aβ) synthesis and secretion in the posterior eye. Aβ is a remarkably penetrative and highly toxic protein that aggressively targets neurons and is a key feature of neurodegenerative disease. In the eye, multiple Aβ reservoirs were discovered in the retinal environment, while elevated Aβ levels were found in the ageing retina and linked with key stages of AMD progression. These findings support the hypothesis that Aβ has a crucial though previously uncharacterised role in driving degenerative processes in the ageing macula.
Here, we bring together the most recent findings emerging from the literature investigating AMD, neurodegeneration, as well as Aβ-structural biology, which support our hypothesis, and offer insights into fundamental degenerative events that could impair the senescent retina. A better understanding of how Aβ might target the retinal function may help in designing novel therapies to treat AMD in the future.
Source: ...