Activation of liver X receptor α protects amyloid β1–40 induced inflammatory and senescent responses in human retinal pigment epithelial cells

Dai, Bingling; Lei, Chunyan; Lin, Rong; Tao, Lifei; Yue, Bin; Peng, Hui

doi:10.1007/s00011-017-1036-4

Cited by 13 publications

(6 citation statements)

References 50 publications

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“…To date, several activating LXR ligands have been reported to modulate lipid metabolism and inflammatory pathways in different injury models, including the eye. Activating LXR with GW3965 has been shown to provide a protective effect in experimental diabetic retinopathy and an inner retinal damage mouse model (56,64), and the LXR agonist TO901317 has been shown to ameliorate amyloid β-induced inflammatory responses in human RPE cells as well as the neural retina (65,66). It is important to note, however, that LXR ligands are not without side effects, most notably temporary hypertriglyceridemia.…”

Section: Discussionmentioning

confidence: 99%

LXRs regulate features of age-related macular degeneration and may be a potential therapeutic target

et al. 2020

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Section: Discussionmentioning

confidence: 99%

LXRs regulate features of age-related macular degeneration and may be a potential therapeutic target

et al. 2020

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“… 30 Moreover, the activation of liver X receptor α (LXR α) and ATP binding cassette subfamily A member 1 (ABCA1) downregulates the expressions of proinflammatory cytokines, such as IL-6 and TNF-α, and suppresses the Aβ-induced inflammatory activity and senescent responses in RPE cells. 31 Intravitreal injection of oligomeric Aβ suppresses the protein expressions of LXR α and ABCA1, which provokes inflammatory activity by upregulation of proinflammatory cytokines. 32 Several medical agents, such as Brimonidine, Puerarin and Baicalin, have been shown to alleviate intracellular pyroptosis and viability damage through preventing Aβ-induced oxidative stress damage and inflammatory activity.…”

Section: Introductionmentioning

confidence: 99%

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

Wang

Jiang

et al. 2021

BMJ Open Ophth

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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.

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“…Nowadays, cell death is classified into two categories: accidental cell death and regulated cell death (RCD) [ 8 ]. Despite previous studies on retina cell damage associated with oxidative stress [ 4 , 9 , 10 ], retina cell death mechanisms are still not fully understood. Many agents have been used to induce retinal cell death, one of which is sodium iodate (SIO), an oxidizer that is toxic to RPE and neuroretina, making it a suitable model for RPE degeneration [ 11 – 13 ].…”

Section: Introductionmentioning

confidence: 99%

Involvement of FSP1-CoQ10-NADH and GSH-GPx-4 pathways in retinal pigment epithelium ferroptosis

et al. 2022

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Retinal pigment epithelium (RPE) degeneration plays an important role in a group of retinal disorders such as retinal degeneration (RD) and age-related macular degeneration (AMD). The mechanism of RPE cell death is not yet fully elucidated. Ferroptosis, a novel regulated cell death pathway, participates in cancer and several neurodegenerative diseases. Glutathione peroxidase 4 (GPx-4) and ferroptosis suppressor protein 1 (FSP1) have been proposed to be two main regulators of ferroptosis in these diseases; yet, their roles in RPE degeneration remain elusive. Here, we report that both FSP1-CoQ10-NADH and GSH-GPx-4 pathways inhibit retinal ferroptosis in sodium iodate (SIO)-induced retinal degeneration pathologies in human primary RPE cells (HRPEpiC), ARPE-19 cell line, and mice. GSH-GPx-4 signaling was compromised after a toxic injury caused by SIO, which was aggravated by silencing GPx-4, and ferroptosis inhibitors robustly protected RPE cells from the challenge. Interestingly, while inhibition of FSP1 caused RPE cell death, which was aggravated by SIO exposure, overexpression of FSP1 effectively protected RPE cells from SIO-induced injury, accompanied by a significant down-regulation of CoQ10/NADH and lipid peroxidation. Most importantly, in vivo results showed that Ferrostatin-1 not only remarkably alleviated SIO-induced RPE cell loss, photoreceptor death, and retinal dysfunction but also significantly ameliorated the compromised GSH-GPx-4 and FSP1-CoQ10-NADH signaling in RPE cells isolated from SIO-induced RPE degeneration. These data describe a distinct role for ferroptosis in controlling RPE cell death in vitro and in vivo and may provide a new avenue for identifying treatment targets for RPE degeneration.

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Activation of liver X receptor α protects amyloid β1–40 induced inflammatory and senescent responses in human retinal pigment epithelial cells

Abstract: Activation of the LXRα-ABCA1 axis may alleviate Aβ induced inflammatory and senescent responses in RPE cells. The beneficial effect appears associated with the inhibition of the NF-κB signaling pathway.

Cited by 13 publications

References 50 publications

LXRs regulate features of age-related macular degeneration and may be a potential therapeutic target

LXRs regulate features of age-related macular degeneration and may be a potential therapeutic target

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

Involvement of FSP1-CoQ10-NADH and GSH-GPx-4 pathways in retinal pigment epithelium ferroptosis

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