Amyloid beta deposition and phosphorylated tau accumulation are key features in aged choroidal vessels in the complement factor H knock out model of retinal degeneration

Aboelnour, Asmaa; Kam, Jaimie Hoh; Elnasharty, Mohamed; Sayed-Ahmed, Ahmed; Jeffery, Glen

doi:10.1016/j.exer.2016.05.015

Cited by 7 publications

(10 citation statements)

References 28 publications

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“…Further evidence to support the role of complement pathway molecule on the choroid comes from animal experiments. In aged mice, there was deposition of amyloid beta and tau proteins in the choroidal arteries, and both amyloid β and phosphorylated tau were expressed at significantly high levels in CFH knockout mice [49]. Amyloid β and phosphorylated Tau in association with brain blood vessels are known to disrupt endothelial cell function; therefore, it is plausible that the accumulation of these proteins results in the disruption of choroidal vessels, potentially thinning the choriocapillaris and thus disrupts outer retinal perfusion.…”

Section: Complement Activation In the Choriocapillarismentioning

confidence: 99%

Asian age-related macular degeneration: from basic science research perspective

Yanagi

Foo

Yoshida

2018

Eye

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In Asian populations, polypoidal choroidal vasculopathy (PCV), a distinct phenotype of neovascular age-related macular degeneration (AMD), is more prevalent than Caucasians. Recently, there has been significant focus on how PCV differs from typical AMD. Although typical AMD and PCV share a variety of mechanisms by which abnormal angiogenic process occurs at the retinochoroidal interface, PCV has different clinical characteristics such as aneurysm-like dilation at the terminal of choroidal neovascular membranes, less frequent drusen and inner choroidal degeneration due to the thickened choroid. Recent studies support an important role for inflammation, angiogenesis molecules and lipid metabolism in the pathogenesis of neovascular AMD. Furthermore, although less attention has been paid to the role of the choroid in AMD, accumulating evidence suggests that the choriocapillaris and choroid also play a pivotal role in drusenogenesis, typical AMD and PCV. This review discusses the basic pathogenic mechanisms of AMD and explores the difference between typical AMD and PCV.

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Section: Complement Activation In the Choriocapillarismentioning

confidence: 99%

Asian age-related macular degeneration: from basic science research perspective

Yanagi

Foo

Yoshida

2018

Eye

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“…[46] In the retina, extracellular deposition of amyloid beta (Aβ) and phosphorylated tau has been seen in normal aging photoreceptor outer segments and BrM. [47484950] Deposition of (Aβ) and phosphorylated tau and their role in small blood vessel damage is widely studied in dementia and neurodegenerative disease. Aβ causes formation of free radicals, leading to vasoconstriction, reduced blood flow and endothelial cell apoptosis,[50] while phosphorylated tau can induce mitochondrial dysfunction.…”

Section: Methodsmentioning

confidence: 99%

“…[47484950] Deposition of (Aβ) and phosphorylated tau and their role in small blood vessel damage is widely studied in dementia and neurodegenerative disease. Aβ causes formation of free radicals, leading to vasoconstriction, reduced blood flow and endothelial cell apoptosis,[50] while phosphorylated tau can induce mitochondrial dysfunction. [50] Aboelnour et al demonstrated increased deposition of Aβ and phosphorylated tau in the choroidal vessels of complement factor H knockout (Cfh _ / _ ) mice, suggesting a relationship of overactive complement to Aβ and tau deposition.…”

Section: Methodsmentioning

confidence: 99%

“…Aβ causes formation of free radicals, leading to vasoconstriction, reduced blood flow and endothelial cell apoptosis,[50] while phosphorylated tau can induce mitochondrial dysfunction. [50] Aboelnour et al demonstrated increased deposition of Aβ and phosphorylated tau in the choroidal vessels of complement factor H knockout (Cfh _ / _ ) mice, suggesting a relationship of overactive complement to Aβ and tau deposition. [50] While both knockout mice and controls showed deposition of Aβ and phosphorylated tau in the choroidal vessels, the increased levels in knockout mice may suggest a role in endothelial cell damage, capillary loss and low perfusion in early AMD.…”

Section: Methodsmentioning

confidence: 99%

“…[50] Aboelnour et al demonstrated increased deposition of Aβ and phosphorylated tau in the choroidal vessels of complement factor H knockout (Cfh _ / _ ) mice, suggesting a relationship of overactive complement to Aβ and tau deposition. [50] While both knockout mice and controls showed deposition of Aβ and phosphorylated tau in the choroidal vessels, the increased levels in knockout mice may suggest a role in endothelial cell damage, capillary loss and low perfusion in early AMD. [50] The presence of Aβ in drusen may also be related to prolonged inflammasome activation in the choroid, leading to increased apoptosis and pyroptosis of RPE cells in AMD.…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Role of the choroid in age-related macular degeneration: A current review

Farazdaghi¹,

Ebrahimi²

2019

J Ophthalmic Vis Res

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Age-related macular degeneration (AMD) is a major cause of vision loss in the developed world and its pathogenesis is a topic of active research. To date, much study has been focused on the role of the retinal pigment epithelium (RPE) and Bruch's membrane (BrM) in AMD pathogenesis, but the role of the choroid has also been investigated. In this review, we focus on recent advancements in research in the role of the choroid in AMD, beginning with an exploration of the histopathologic, cellular and molecular changes that occur in the choroid in AMD and concluding by discussing new choroidal imaging techniques and patterns seen on fluorescein angiography, indocyanine green angiography, spectral-domain optical coherence tomography and optical coherence tomography angiography. Exploring these domains will lead to a better understanding of the factors at play beyond the outer retina in this important disease.

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Sialylation acts as a checkpoint for innate immune responses in the central nervous system

Klaus

Liao

Allendorf

et al. 2020

Glia

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Sialic acids are monosaccharides that normally terminate the glycan chains of cell surface glyco‐proteins and ‐lipids in mammals, and are highly enriched in the central nervous tissue. Sialic acids are conjugated to proteins and lipids (termed “sialylation”) by specific sialyltransferases, and are removed (“desialylation”) by neuraminidases. Cell surface sialic acids are sensed by complement factor H (FH) to inhibit complement activation or by sialic acid‐binding immunoglobulin‐like lectin (SIGLEC) receptors to inhibit microglial activation, phagocytosis, and oxidative burst. In contrast, desialylation of cells enables binding of the opsonins C1, calreticulin, galectin‐3, and collectins, stimulating phagocytosis of such cells. Hypersialylation is used by bacteria and cancers as camouflage to escape immune recognition, while polysialylation of neurons protects synapses and neurogenesis. Insufficient lysosomal cleavage of sialylated molecules can lead to lysosomal accumulation of lipids and aggregated proteins, which if excessive may be expelled into the extracellular space. On the other hand, desialylation of immune receptors can activate them or trigger removal of proteins. Loss of inhibitory SIGLECs or FH triggers reduced clearance of aggregates, oxidative brain damage and complement‐mediated retinal damage. Thus, cell surface sialylation recognized by FH, SIGLEC, and other immune‐related receptors acts as a major checkpoint inhibitor of innate immune responses in the central nervous system, while excessive cleavage of sialic acid residues and consequently removing this checkpoint inhibitor may trigger lipid accumulation, protein aggregation, inflammation, and neurodegeneration.

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Amyloid beta deposition and phosphorylated tau accumulation are key features in aged choroidal vessels in the complement factor H knock out model of retinal degeneration

Cited by 7 publications

References 28 publications

Asian age-related macular degeneration: from basic science research perspective

Asian age-related macular degeneration: from basic science research perspective

Role of the choroid in age-related macular degeneration: A current review

Sialylation acts as a checkpoint for innate immune responses in the central nervous system

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