Inflammasome priming increases retinal pigment epithelial cell susceptibility to lipofuscin phototoxicity by changing the cell death mechanism from apoptosis to pyroptosis

Brandstetter, Carolina; Patt, Joshua C.; Holz, Frank G.; Krohne, Tim U.

doi:10.1016/j.jphotobiol.2016.05.018

Cited by 55 publications

(38 citation statements)

References 28 publications

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“…The downexpression of HSPA1A could be explained considering the reduction of the synthesis of proteins substrate of Hsp70. [48,[150][151][152][153][154][155][156][157][158][159][160][161][162][163] SMALL GTPASE SUPERFAMILY ALTERED SIGNALLING Under stress conditions KRAS (already known to be involved in Noonan syndrome) upregulation could determine an uncontrolled RPE cell proliferation or functional alterations.…”

Section: Retinoic Acid Cycle (Rdh5 Mkv)mentioning

confidence: 99%

RETRACTED ARTICLE: Role of oxidative stress in Retinitis pigmentosa: new involved pathways by an RNA-Seq analysis

et al. 2018

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Retinitis pigmentosa (RP) is a very heterogeneous inherited ocular disorder group characterized by progressive retinal disruption. Retinal pigment epithelium (RPE) degeneration, due to oxidative stress which arrests the metabolic support to photoreceptors, represents one of the principal causes of RP. Here, the role of oxidative stress in RP onset and progression was analyzed by a comparative whole transcriptome analysis of human RPE cells, treated with 100 µg/ml of oxLDL and untreated, at different time points. Experiment was thrice repeated and performed on Ion Proton TM sequencing system. Data analysis, including low quality reads trimming and gene expression quantification, was realized by CLC Genomics Workbench software. The whole analysis highlighted 14 clustered "macro-pathways" and many sub-pathways, classified by selection of 5271 genes showing the highest alteration of expression. Among them, 23 genes were already known to be RP causative ones (15 over-expressed and 8 down-expressed), and their enrichment and intersection analyses highlighted new 77 candidate related genes (49 over-expressed and 28 down-expressed). A final filtering analysis then highlighted 29 proposed candidate genes. This data suggests that many new genes, not yet associated with RP, could influence its etiopathogenesis.

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Section: Retinoic Acid Cycle (Rdh5 Mkv)mentioning

confidence: 99%

RETRACTED ARTICLE: Role of oxidative stress in Retinitis pigmentosa: new involved pathways by an RNA-Seq analysis

et al. 2018

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“…Likewise, Brandstetter et al have recently shown that C5a acts as a priming signal for RPE cell inflammasome activation with IL-1β secretion after lipofuscin mediated photo-oxidative damage (Brandstetter et al, 2015). This same group also showed that C5a can activate the inflammasome in RPE cells, which increases its susceptibility to photo-oxidative mediated cell death through pyroptosis (Brandstetter et al, 2016). Finally, sublytic C5b-9 is known to activate the inflammasome (Laudisi et al, 2013; Triantafilou et al, 2013), providing an additional possible link between complement and inflammasome activation.…”

Section: The Role Of Inflammation On the Rpementioning

confidence: 96%

The impact of oxidative stress and inflammation on RPE degeneration in non-neovascular AMD

Datta

Cano

Ebrahimi

et al. 2017

Progress in Retinal and Eye Research

593

487

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The retinal pigment epithelium (RPE) is a highly specialized, unique epithelial cell that interacts with photoreceptors on its apical side and with Bruch’s membrane and the choriocapillaris on its basal side. Due to vital functions that keep photoreceptors healthy, the RPE is essential for maintaining vision. With aging and the accumulated effects of environmental stresses, the RPE can become dysfunctional and die. This degeneration plays a central role in age-related macular degeneration (AMD) pathobiology, the leading cause of blindness among the elderly in western societies. Oxidative stress and inflammation have both physiological and potentially pathological roles in RPE degeneration. Given the central role of the RPE, this review will focus on the impact of oxidative stress and inflammation on the RPE with AMD pathobiology. Physiological sources of oxidative stress as well as unique sources from photo-oxidative stress, the phagocytosis of photoreceptor outer segments, and modifiable factors such as cigarette smoking and high fat diet ingestion that can convert oxidative stress into a pathological role, and the negative impact of impairing the cytoprotective roles of mitochondrial dynamics and the Nrf2 signaling system on RPE health in AMD will be discussed. Likewise, the response by the innate immune system to an inciting trigger, and the potential role of local RPE production of inflammation, as well as a potential role for damage by inflammation with chronicity if the inciting trigger is not neutralized, will be debated.

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“…There is evidence showing the ability of drusen to induce the activation of inflammasome, namely NLRP3 inflammasome, in retinal mononuclear cells 20 . Inflammasome has been detected in the RPE, in both dry and wet AMD, and might contribute to RPE degeneration 21 , 22 . Interestingly, factors released from reactive microglia can also induce the activation of NLRP3 inflammasome in ARPE-19 cells 9 .…”

Section: Introductionmentioning

confidence: 99%

Blockade of microglial adenosine A2A receptor impacts inflammatory mechanisms, reduces ARPE-19 cell dysfunction and prevents photoreceptor loss in vitro

Madeira

Rashid

Ambrósio

et al. 2018

Sci Rep

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Age-related macular degeneration (AMD) is characterized by pathological changes in the retinal pigment epithelium (RPE) and loss of photoreceptors. Growing evidence has demonstrated that reactive microglial cells trigger RPE dysfunction and loss of photoreceptors, and inflammasome pathways and complement activation contribute to AMD pathogenesis. We and others have previously shown that adenosine A2A receptor (A2AR) blockade prevents microglia-mediated neuroinflammatory processes and mediates protection to the retina. However, it is still unknown whether blocking A2AR in microglia protects against the pathological features of AMD. Herein, we show that an A2AR antagonist, SCH58261, prevents the upregulation of the expression of pro-inflammatory mediators and the alterations in the complement system triggered by an inflammatory challenge in human microglial cells. Furthermore, blockade of A2AR in microglia decreases the inflammatory response, as well as complement and inflammasome activation, in ARPE-19 cells exposed to conditioned medium of activated microglia. Finally, we also show that blocking A2AR in human microglia increases the clearance of apoptotic photoreceptors. This study opens the possibility of using selective A2AR antagonists in therapy for AMD, by modulating the interplay between microglia, RPE and photoreceptors.

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Inflammasome priming increases retinal pigment epithelial cell susceptibility to lipofuscin phototoxicity by changing the cell death mechanism from apoptosis to pyroptosis

Cited by 55 publications

References 28 publications

RETRACTED ARTICLE: Role of oxidative stress in Retinitis pigmentosa: new involved pathways by an RNA-Seq analysis

RETRACTED ARTICLE: Role of oxidative stress in Retinitis pigmentosa: new involved pathways by an RNA-Seq analysis

The impact of oxidative stress and inflammation on RPE degeneration in non-neovascular AMD

Blockade of microglial adenosine A2A receptor impacts inflammatory mechanisms, reduces ARPE-19 cell dysfunction and prevents photoreceptor loss in vitro

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