Role of amyloid β-peptide in the pathogenesis of age-related macular degeneration

Abstract

Age-related macular degeneration (AMD) is the most common eye disease in elderly patients, which could lead to irreversible vision loss and blindness. Increasing evidence indicates that amyloid β-peptide (Aβ) might be associated with the pathogenesis of AMD. In this review, we would like to summarise the current findings in this field. The literature search was done from 1995 to Feb, 2021 with following keywords, ‘Amyloid β-peptide and age-related macular degeneration’, ‘Inflammation and age-related macular degeneration’, ‘Angiogenesis and age-related macular degeneration’, ‘Actin cytoskeleton and amyloid β-peptide’, ‘Mitochondrial dysfunction and amyloid β-peptide’, ‘Ribosomal dysregulation and amyloid β-peptide’ using search engines Pubmed, Google Scholar and Web of Science. Aβ congregates in subretinal drusen of patients with AMD and participates in the pathogenesis of AMD through enhancing inflammatory activity, inducing mitochondrial dysfunction, altering ribosomal function, regulating the lysosomal pathway, affecting RNA splicing, modulating angiogenesis and modifying cell structure in AMD. The methods targeting Aβ are shown to inhibit inflammatory signalling pathway and restore the function of retinal pigment epithelium cells and photoreceptor cells in the subretinal region. Targeting Aβ may provide a novel therapeutic strategy for AMD.

An Essential Role for Alzheimer’s-Linked Amyloid Beta Oligomers in Neurodevelopment: Transient Expression of Multiple Proteoforms during Retina Histogenesis

“…Second, it remains to be seen whether the retina of humans expresses AβOs in various degenerative pathologies. This possibility is consistent with reports linking Aβ to neurodegenerative disorders of the retina, not only AD [124] but also macular degeneration and glaucoma [124][125][126][127]. In addition, experimental type diabetes in rabbits, another species which has the human Aβ42 sequence, has been shown to induce retina AβOs [128].…”

Carnosine Counteracts the Molecular Alterations Aβ Oligomers-Induced in Human Retinal Pigment Epithelial Cells

“…Of note, AD has been associated with AMD. In particular, it has been demonstrated that Aβ oligomers are involved in AMD pathogenesis [4,29], with the extracellular deposits of these species leading to the formation of drusen [5]. Additionally, AD and AMD share common pathophysiological features, including oxidative stress and neuroinflammation [8,9].…”

“…In fact, vision-related alterations are common in AD, and visual defects are due to either degeneration of the visual cortex or to retinal degeneration associated with glaucoma and AMD. Several pieces of evidence indicate that the oligomeric form of amyloid-β (Aβ) peptide, one of the main actors in AD-related neurodegeneration, might be associated with AMD pathogenesis [4]. In particular, Aβ aggregates constitute the drusen deposits, resulting in chronic low-level inflammation and impairment of the retinal barrier [5].…”

Endogenous and Exogenous Regulation of Redox Homeostasis in Retinal Pigment Epithelium Cells: An Updated Antioxidant Perspective

“…VEGF expression in the RPE is significantly increased by the synergistic action of TGFβ2 and TNFα, as well as that of TGFβ2 and thrombin [ 125 , 216 , 217 , 218 ]. Increased ROS production by mitochondria also contributes to the accumulation of the amyloid β protein and leads to the excessive secretion of VEGF [ 219 ].…”

“…Simultaneously, nitric oxide inactivates the PP2A catalytic subunit, which leads to increased phosphorylation of vimentin, which is a substrate for this phosphatase [ 248 ]. OS-mediated accumulation of Aβ induces inflammatory activity, oxidative phosphorylation dysregulation, angiogenesis, and cytoskeleton destabilization, causing a large amount of damage in the subretinal region, which is associated with the pathogenesis of AMD [ 219 , 249 ]. Aβ dislocates occludin and decreases the levels of occludin and zonula occludens-1 mRNA expression in RPE cells.…”