Drusen and Pro-inflammatory Mediators in the Post-Mortem Human Eye

Jiang, Kailun; To, Eleanor; Cui, Jing; Cao, Siyang

doi:10.4172/2155-9570-3-208

Cited by 6 publications

(10 citation statements)

References 30 publications

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“…6) shown here. Interestingly, CXCL11 is more highly expressed in younger eyes (<57 yrs) compared to older eyes (>70 yrs), and particularly those younger eyes with drusen as shown in our recent study on postmortem eyes [32]. It is possible that this gene is one of the first responders to the gradual AGE accumulation in the outer retina in eyes with drusen, and is a novel gene of interest for its potential involvement in early stages of outer retinal dysfunction and AMD progression.…”

Section: Novel Genes: Cxcl11 and Rsad2mentioning

confidence: 62%

“…It is associated with inflammatory responses and abnormal lipid accumulation. Interestingly, RSAD2 was also up-regulated in RPE cells in response to stimulation with amyloid-β [11] and it was shown to co-localize with drusen and outer retina sites in human postmortem eyes [32]. RSAD2 and its function in the retina warrants further attention and may be a candidate marker of inflammatory events in the outer retina.…”

Section: Novel Genes: Cxcl11 and Rsad2mentioning

confidence: 97%

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Parainflammation associated with advanced glycation endproduct stimulation of RPE in vitro: Implications for age-related degenerative diseases of the eye

et al. 2013

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Age related macular degeneration (AMD) is one of the leading causes of blindness in Western society. A hallmark of early stage AMD are drusen, extracellular deposits that accumulate in the outer retina. Advanced glycation endproducts (AGE) accumulate with aging and are linked to several age-related diseases such as Alzheimer's disease, osteoarthritis, atherosclerosis and AMD. AGE deposits are found in drusen and in Bruch's membrane of the eye and several studies have suggested its role in promoting oxidative stress, apoptosis and lipofuscin accumulation. Recently, complement activation and chronic inflammation have been implicated in the pathogenesis of AMD. While AGEs have been shown to promote inflammation in other diseases, whether it plays a similar role in AMD is not known. This study investigates the effects of AGE stimulation on pro- and anti-inflammatory pathways in primary culture of human retinal pigment epithelial cells (RPE). Differential gene expression studies revealed a total of 41 up- and 18 down-regulated RPE genes in response to AGE stimulation. These genes fell into three categories as assessed by gene set enrichment analysis (GSEA). The main categories were inflammation (interferon-induced, immune response) and proteasome degradation, followed by caspase signaling. Using suspension array technology, protein levels of secreted cytokines and growth factors were also examined. Anti-inflammatory cytokines including IL10, IL1ra and IL9 were all overexpressed. Pro-inflammatory cytokines including IL4, IL15 and IFN-γ were overexpressed, while other pro-inflammatory cytokines including IL8, MCP1, IP10 were underexpressed after AGE stimulation, suggesting a para-inflammation state of the RPE under these conditions. Levels of mRNA of chemokine, CXCL11, and viperin, RSAD2, were up-regulated and may play a role in driving the inflammatory response via the NF-kB and JAK-STAT pathways. CXCL11 was strongly immunoreactive and associated with drusen in the AMD eye. The pathways and novel genes identified here highlight inflammation as a key response to AGE stimulation in primary culture of human RPE, and identify chemokine CXCL11 as putative novel agent associated with the pathogenesis of AMD.

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Section: Novel Genes: Cxcl11 and Rsad2mentioning

confidence: 62%

Section: Novel Genes: Cxcl11 and Rsad2mentioning

confidence: 97%

Parainflammation associated with advanced glycation endproduct stimulation of RPE in vitro: Implications for age-related degenerative diseases of the eye

et al. 2013

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“…W ostatnim czasie podkreśla się rolę zapalenia jako istotnego czynnika biorącego udział w biogenezie druz (7,8). Dowodem na to jest obecność w druzach białek układu dopełniacza oraz elementów układu immunologicznego.…”

Section: Issn 0023-2157 Index 362646unclassified

“…Histochemiczna analiza druz wykazała obecność składowych dopełniacza: C3, C5, C5b-9, kompleksu atakującego błonę (ang. Complement Membrane Attack Complex -MAC) oraz lekkich łańcuchów immunoglobulin (7,8). Reakcje zapalne towarzyszące druzom są analogiczne do tych, które występują np.…”

Section: Issn 0023-2157 Index 362646unclassified

Characterizing drusen using modern multimodal imaging of the retina

Karska‐Basta¹,

Chrząszcz²,

Kubicka‐Trząska³

et al. 2018

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Druzy po raz pierwszy zostały opisane w 1855 roku przez Franciscusa Dondersa, który nazwał je wówczas kulkami koloidowymi ("colloid kugeln") (1). Rok później Heinrich Müller, niemiecki anatom, nazwał je druzami ("drusen") (2). Druzy to złogi nierozpuszczalnego materiału, będącego nagromadzeniem produktów przemiany materii komórek fotoreceptorowych siatkówki, umiejscowione między warstwą komórek nabłonka barwnikowego siatkówki (ang. Retinal Pigment Epithelium-RPE) a błoną Brucha. Druzy pojawiają się wraz ze starzeniem się narządu wzroku oraz są charaktery

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“…Many components of drusen have been identified however the details of drusen biogenesis continue to be sought for molecular insights into AMD prevention and therapy. Histochemical and immunohistochemical studies have shown that drusen contain a variety of lipids, polysaccharides, glycosaminoglycans and proteins (Abdelsalam et al 1999;Hageman et al 1999Hageman et al , 2001Kamei and Hollyfield 1999;Mullins et al 2000;Malek et al 2003;Anderson et al 2004;Curcio et al 2005a,b;Luibl et al 2006;Wang et al 2010;Jiang et al 2012). Proteomic studies, both qualitative and quantitative, have expanded the repertoire of proteins and protein modifications associated with drusen (Crabb et al 2002a;Umeda et al 2005;Yuan et al 2010;Garland et al 2013).…”

mentioning

confidence: 99%

The Proteomics of Drusen

Crabb

2014

Cold Spring Harbor Perspectives in Medicine

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Drusen and Pro-inflammatory Mediators in the Post-Mortem Human Eye

Cited by 6 publications

References 30 publications

Parainflammation associated with advanced glycation endproduct stimulation of RPE in vitro: Implications for age-related degenerative diseases of the eye

Parainflammation associated with advanced glycation endproduct stimulation of RPE in vitro: Implications for age-related degenerative diseases of the eye

Characterizing drusen using modern multimodal imaging of the retina

The Proteomics of Drusen

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