Aβ-Induced Senescent Retinal Pigment Epithelial Cells Create a Proinflammatory Microenvironment in AMD

Cao, Lining; Wang, Hao; Wang, Fang; Xu, Dongmei; Liu, Fang; Liu, Chaoqi

doi:10.1167/iovs.13-11612

Cited by 62 publications

(57 citation statements)

References 79 publications

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“…This finding is consistent with our previous in vitro study, indicating that Aβ peptide is involved in the senescence of RPE cells (19). It is also consistent with the results of other studies, suggesting that Aβ peptides induce endothelial cells, astrocytes and neurons to enter senescence (15,17,18).…”

Section: Discussionsupporting

confidence: 93%

“…Our previous study (19) and the present study indicate that Aβ-induced senescent RPE cells may constitute a link between chronic inflammation and neuroretinal degeneration. Senescence-causing inducers, such as DNA damage, protein aggregation and increased ROS may activate the p53 and p16…”

Section: Discussionsupporting

confidence: 73%

“…Aβ(1-42) peptide and its inactive reverse control peptide Aβ(42-1) were prepared as described in our previous study (19). Briefly, 0.5 mg of lyophilized Aβ peptide (Sigma-Aldrich, Shanghai, China) was dissolved in 140 µl hexafluoroisopropanol (HFIP) and incubated for 20 min, followed by the addition of 900 µl distilled H 2 O and a 20-min incubation in the HFIP/water mixture.…”

Section: Methodsmentioning

confidence: 99%

“…Subsequently, the solvent was evaporated from the resulting supernatant under constant stirring at room temperature for 5 days. Oligomerization was verified by dot blot assay as previously described (19).…”

Section: Methodsmentioning

confidence: 99%

“…Aβ has been recently been shown to be involved in the senescence of neuronal cells, astrocytes and endothelial cells (15)(16)(17)(18). Our previous in vitro study demonstrated that Aβ peptide caused RPE cells to enter senescence (19). However, the in vivo effects of Aβ peptide on RPE cell senescence and senescence-associated inflammation remain unclear.…”

Section: Introductionmentioning

confidence: 98%

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Subretinal injection of amyloid-β peptide accelerates RPE cell senescence and retinal degeneration

Liu

Cao

Yang

et al. 2014

International Journal of Molecular Medicine

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Abstract. Drusen are considered a hallmark characteristic of age-related macular degeneration (AMD). In our previous study, we found that amyloid-β (Aβ) peptide, a component of drusen, induced the cells of the retinal pigment epithelium (RPE; RPE cells) to enter senescence; however, its effects in vivo remain unknown. Thus, the present study was carried out to explore the in vivo effects of Aβ peptide on RPE cell senescence and senescence-associated inflammation in C57BL/6 mice. C57BL/6 mice received a subretinal injection of Aβ(1-42) peptide; on day 7 post-injection, the mice were anesthetized and subjected to whole-body perfusion with 4% paraformaldehyde (PFA) in PBS and the whole eyes were then enucleated. Retinal function was assessed by electroretinography (ERG), and the morphological characteristics of the retina were examined by light and electron microscopy. Fundus autofluorescence (FAF) was examined by confocal scanning laser ophthalmoscopy (cSLO). The expression of p16INK4a , a marker of cellular senescence, was examined by immunofluorescence staining and western blot analysis. The RPE-choroid was analyzed for cytokine expression by RT-PCR. In Aβ(1-42)-injected mice, scotopic ERG responses declined. Degenerative alterations, including the disruption of the inner segment (IS)/outer segment (OS) junction and extensive vacuolation and thickness of Bruch's membrane (BrM) were observed under a a light microscope. The accumulation of vacuoles and the loss of basal infoldings in the RPE were identified using an electron microscope. FAF and p16INK4a expression increased in Aβ(1-42)-injected mice. In addition, Aβ(1-42) upregulated interleukin (IL)-6 and IL-8 gene expression in the RPE-choroid. In conclusion, our results confirm the effects of Aβ(1-42) peptide on RPE senescence in vivo. The Aβ-injected mice developed AMD-like ocular pathology. It is thus suggested that RPE cell senescence is a potential mechanistic link between inflammation and retinal degeneration.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 73%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

See 3 more Smart Citations

Subretinal injection of amyloid-β peptide accelerates RPE cell senescence and retinal degeneration

Liu

Cao

Yang

et al. 2014

International Journal of Molecular Medicine

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Amyloid β induces NLRP3 inflammasome activation in retinal pigment epithelial cells via NADPH oxidase‐ and mitochondria‐dependent ROS production

Wang¹,

Yao

Zhu³

et al. 2016

J Biochem & Molecular Tox

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Amyloid β (Aβ)-induced chronic inflammation is believed to be a key pathogenic process in early-stage age-related macular degeneration (AMD). Nucleotide oligomerization domain (NOD)-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome activation triggered by Aβ is responsible for retinal pigment epithelium (RPE) dysfunction in the onset of AMD; however, the detailed molecular mechanism remains unclear. In this study, we investigated the involvement of NADPH oxidase- and mitochondria-derived reactive oxygen species (ROS) in the process of Aβ -induced NLRP3 inflammasome activation in LPS-primed ARPE-19 cells. The results showed that Aβ could induce excessive ROS generation, MAPK/NF-κB signaling activation and subsequently NLRP3 inflammasome activation in LPS-primed ARPE-19 cells. Furthermore, the inductive effect of Aβ on NLRP3 inflammasome activation was mediated in a manner dependent on NADPH oxidase- and mitochondria-derived ROS. Our findings may provide a novel insight into the molecular mechanism by which Aβ contributes to the early-stage AMD.

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Retinal Pigment Epithelium in Proliferative Disorders

Dik

Bastiaans

Meurs

2020

Retinal Pigment Epithelium in Health and Disease

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Aβ-Induced Senescent Retinal Pigment Epithelial Cells Create a Proinflammatory Microenvironment in AMD

Abstract: The altered secretory phenotype of senescent RPE cells may contribute to age-related inflammation in AMD. Chinese Abstract.

Cited by 62 publications

References 79 publications

Subretinal injection of amyloid-β peptide accelerates RPE cell senescence and retinal degeneration

Subretinal injection of amyloid-β peptide accelerates RPE cell senescence and retinal degeneration

Amyloid β induces NLRP3 inflammasome activation in retinal pigment epithelial cells via NADPH oxidase‐ and mitochondria‐dependent ROS production

Retinal Pigment Epithelium in Proliferative Disorders

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