Regulation of Ocular Inflammation â What Experimental and Human Studies have Taught Us

Smet, Marc D. de

doi:10.1016/s1350-9462(01)00011-8

Cited by 75 publications

(16 citation statements)

References 286 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CD4 + T cells are increased in number and activated in intraocular fluids from patients with uveitis and in several animal models of uveitis [8]. Despite these studies, the mechanism of CD4 + T lymphocyte-mediated inflammation in uveitis is not fully understood.…”

Section: Introductionmentioning

confidence: 99%

Interleukin-17 causes neutrophil mediated inflammation in ovalbumin-induced uveitis in DO11.10 mice

Zhang¹,

Zhong²,

Spencer³

et al. 2009

Cytokine

View full text Add to dashboard Cite

T cell-mediated uveitis is strongly associated with many systemic inflammatory disorders. Th17 cells are a novel T cell subset characterized by production of interleukin (IL)-17. In this study, we used DO11.10 mice to investigate the role of IL-17 in the pathogenesis of uveitis. CD4 + T cells in DO11.10 mice are genetically engineered to react with ovalbumin (OVA). IL-17 expression was determined by real-time PCR and ELISPOT. Uveitis was induced by intravitreal injection of OVA, and ocular inflammation was evaluated by intravital microscopy. OVA challenge significantly induced IL-17 production by DO11.10 splenocytes in vitro. Next, we examined whether OVA challenge could elicit local inflammation and induce IL-17 in vivo. OVA elicited marked neutrophil-predominant inflammatory cell infiltration in the eyes. This leukocyte influx was mediated by CD4 + lymphocytes as evidenced by significant inhibition of the ocular inflammation by CD4+ depleting antibody. Compared to control mice, OVA treatment induced IL-17 expression. Moreover, anti-IL-17 antibody markedly reduced OVA-mediated ocular inflammation. Finally, the neutralization of IL-17 attenuated ocular expression of CXCL2 and CXCL5, two cytokines which are chemotactic for neutrophils. Our study suggests that IL-17 is implicated in the pathogenesis of this T cell-mediated model of uveitis in part through neutrophil chemotaxis as a downstream effect of IL-17.

show abstract

Section: Introductionmentioning

confidence: 99%

Interleukin-17 causes neutrophil mediated inflammation in ovalbumin-induced uveitis in DO11.10 mice

Zhang¹,

Zhong²,

Spencer³

et al. 2009

Cytokine

View full text Add to dashboard Cite

show abstract

“…For example, less than a third of uveitis patients tested will have T cell responses to arrestin, or S-antigen, the most recognized autoantigen for uveitis in humans (10). In addition, susceptibility to the two most important antigens used to induce experimental animal uveitis, interphotoreceptor retinoid-binding protein (IRBP) and S-antigen, varies from species to species despite evolutionarily conserved structures (11) and documented T cell response from uveitis patients to IRBP has been scarce. Recent work has also indicated that, similar to multiple sclerosis (MS), Th17 cells may be one of key immune components that contribute to the molecular pathogenesis of autoimmune uveitis (12).…”

Section: Introductionmentioning

confidence: 99%

Gene Expression Profiling in Autoimmune Noninfectious Uveitis Disease

Li¹,

Liu²,

Maminishkis

et al. 2008

The Journal of Immunology

View full text Add to dashboard Cite

Noninfectious uveitis is a predominantly T cell-mediated autoimmune, intraocular inflammatory disease. To characterize the gene expression profile from patients with noninfectious uveitis, PBMCs were isolated from 50 patients with clinically characterized noninfectious uveitis syndrome. A pathway-specific cDNA microarray was used for gene expression profiling and real-time PCR array for further confirmation. Sixty-seven inflammation- and autoimmune-associated genes were found differentially expressed in uveitis patients, with 28 of those genes being validated by real-time PCR. Several genes previously unknown for autoimmune uveitis, including IL-22, IL-19, IL-20, and IL-25/IL-17E, were found to be highly expressed among uveitis patients compared with the normal subjects with IL-22 expression highly variable among the patients. Furthermore, we show that IL-22 can affect primary human retinal pigment epithelial cells by decreasing total tissue resistance and inducing apoptosis possibly by decreasing phospho-Bad level. In addition, the microarray data identified a possible uveitis-associated gene expression pattern, showed distinct gene expression profiles in patients during periods of clinical activity and quiescence, and demonstrated similar expression patterns in related patients with similar clinical phenotypes. Our data provide the first evidence that a subset of IL-10 family genes are implicated in noninfectious uveitis and that IL-22 can affect human retinal pigment epithelial cells. The results may facilitate further understanding of the molecular mechanisms of autoimmune uveitis and other autoimmune originated inflammatory diseases.

show abstract

“…Essentially all patients are HLA-A29 positive, which represents the strongest associations between an HLA class I allele and human disease[35,36]. Nevertheless, the role of HLA-A29 has not yet been elucidated and consequently the pathophysiology of BU is not well understood[1].…”

Section: Discussionmentioning

confidence: 99%

Aberrant leukocyte telomere length in Birdshot Uveitis

et al. 2017

View full text Add to dashboard Cite

PurposeBirdshot Uveitis (BU) is an archetypical chronic inflammatory eye disease, with poor visual prognosis, that provides an excellent model for studying chronic inflammation. BU typically affects patients in the fifth decade of life. This suggests that it may represent an age-related chronic inflammatory disease, which has been linked to increased erosion of telomere length of leukocytes.MethodsTo study this in detail, we exploited a sensitive standardized quantitative real-time polymerase chain reaction to determine the peripheral blood leukocyte telomere length (LTL) in 91 genotyped Dutch BU patients and 150 unaffected Dutch controls.ResultsAlthough LTL erosion rates were very similar between BU patients and healthy controls, we observed that BU patients displayed longer LTL, with a median of log (LTL) = 4.87 (= 74131 base pair) compared to 4.31 (= 20417 base pair) in unaffected controls (P<0.0001). The cause underpinning the difference in LTL could not be explained by clinical parameters, immune cell-subtype distribution, nor genetic predisposition based upon the computed weighted genetic risk score of genotyped validated variants in TERC, TERT, NAF1, OBFC1 and RTEL1.ConclusionsThese findings suggest that BU is accompanied by significantly longer LTL.

show abstract

Regulation of Ocular Inflammation â What Experimental and Human Studies have Taught Us

Cited by 75 publications

References 286 publications

Interleukin-17 causes neutrophil mediated inflammation in ovalbumin-induced uveitis in DO11.10 mice

Interleukin-17 causes neutrophil mediated inflammation in ovalbumin-induced uveitis in DO11.10 mice

Gene Expression Profiling in Autoimmune Noninfectious Uveitis Disease

Aberrant leukocyte telomere length in Birdshot Uveitis

Contact Info

Product

Resources

About

Regulation of Ocular Inflammation â What Experimental and Human Studies have Taught Us

Cited by 75 publications

References 286 publications

Interleukin-17 causes neutrophil mediated inflammation in ovalbumin-induced uveitis in DO11.10 mice

Interleukin-17 causes neutrophil mediated inflammation in ovalbumin-induced uveitis in DO11.10 mice

Gene Expression Profiling in Autoimmune Noninfectious Uveitis Disease

Aberrant leukocyte telomere length in Birdshot Uveitis

Contact Info

Product

Resources

About

Regulation of Ocular Inflammation â What Experimental and Human Studies have Taught Us