Simultaneous Analysis of Multiple Cytokines in the Vitreous of Patients with Sarcoid Uveitis

Nagata, Kenji; Maruyama, Kouichi; Uno, Kazuko; Shinomiya, Katsuhiko; Yoneda, Kazuhito; Hamuro, Junji; Sugita, Sunao; Yoshimura, Takeru; Sonoda, Koh Hei; Mochizuki, Manabu; Kinoshita, Shigeru

doi:10.1167/iovs.11-9244

Cited by 46 publications

(54 citation statements)

References 34 publications

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“…In the present study, although there was no significant difference in vitreous IL-4 level between the ocular sarcoidosis group and the idiopathic ERM group, vitreous levels of IL-6, IL-10, IFN-c, and TNFa were significantly elevated in the ocular sarcoidosis group compared with the idiopathic ERM group (Fig. 5), consistent with the report of Nagata et al 40 We previously demonstrated that serum CXCL9 and CXCL10 levels are markedly augmented in patients with ocular sarcoidosis compared with healthy subjects. These results indicate a role of CXCL9 and CXCL10 in the mechanisms that account for migration of CXCR3-expressing activated Th1 cells to the eye.…”

Section: Discussionsupporting

confidence: 92%

“…36,37 The CD4/CD8 ratio of T cells infiltrating the vitreous is elevated in ocular sarcoidosis compared with other etiologies of uveitis, 38 and T-cell clones established from the vitreous T cells of ocular sarcoidosis patients produce a large amount of inflammatory cytokines including IL-1a, IL-6, and IL-8. 39 Nagata et al 40 reported that vitreous levels of IL-1ra, IL-4, IL-5, IL-6, IL-8, IL-9, IL10, IL-12, IFN-c, and TNFa were elevated in ocular sarcoidosis patients compared with idiopathic ERM patients. In the present study, although there was no significant difference in vitreous IL-4 level between the ocular sarcoidosis group and the idiopathic ERM group, vitreous levels of IL-6, IL-10, IFN-c, and TNFa were significantly elevated in the ocular sarcoidosis group compared with the idiopathic ERM group (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…However, a previous study also observed no increase in vitreous IL-17A level in ocular sarcoidosis. 40 It is possible that Th17 cells do not play a pivotal role in the development of ocular inflammation in sarcoidosis with granulomatous formation.…”

Section: Discussionmentioning

confidence: 99%

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Association of High-Mobility Group Box-1 With Th Cell–Related Cytokines in the Vitreous of Ocular Sarcoidosis Patients

Takeuchi

Taguchi

Sato

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. High-mobility group box-1 (HMGB1) is a nonhistone DNA-binding nuclear protein released from necrotic cells, which is also secreted by activated leukocytes and acts as a primary proinflammatory cytokine. In this study, we compared vitreous HMGB1 levels in ocular sarcoidosis with those in noninflammatory vitreoretinal diseases and evaluated its association with Th cell-related and proinflammatory cytokines. RESULTS. High-mobility group box-1 was detected in the vitreous of 23 of 24 patients (95.8%) with ocular sarcoidosis. Mean vitreous level of HMGB1 was the highest in the sarcoidosis group, followed by the PDR and ERM groups, with significant differences between the three groups. In the sarcoidosis group, vitreous levels of IL-6, IL-10, IL-31, IFN-c, sCD40L, and TNFa were significantly higher than those in the idiopathic ERM group, and IFN-c and sCD40L were significantly higher than those in the PDR group. Vitreous HMGB-1 level correlated significantly with IL-10, IFN-c, and sCD40L levels but not with IL-6, IL-17, IL-31, or TNFa levels.CONCLUSIONS. The vitreous level of HMGB1 is elevated in ocular sarcoidosis and is associated with vitreous levels of Th1-and regulatory T-related cytokines, but not with proinflammatory or Th17-related cytokines.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

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Association of High-Mobility Group Box-1 With Th Cell–Related Cytokines in the Vitreous of Ocular Sarcoidosis Patients

Takeuchi

Taguchi

Sato

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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“…In addition, we have confirmation of our data in that at least some of our measured vitreal cytokine levels show levels that are comparable to already published data using the Bio-Plex technique (i.e., for IL-1b, IL-4, IL-8, and TNF-a). 15,21,22 Vitreomacular interface disorders, such as vitreomacular traction, can result in the formation of MHs. The persistence of such a disturbance can lead to the growth of ERMs, which may or may not be associated with the formation of MHs.…”

Section: Discussionmentioning

confidence: 99%

Vitreal Cytokine Profile Differences Between Eyes With Epiretinal Membranes or Macular Holes

Zandi

Tappeiner

Pfister

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Cytokines play an important role in cell signaling in inflammatory and repair processes, also within the posterior segment of the eye. These molecules are thus implicated in the pathophysiology of several vitreoretinal diseases. In the present study, we compared vitreal cytokine profiles in patients with idiopathic epiretinal membranes (ERMs) and idiopathic full-thickness macular holes (MHs) without epiretinal membranes.METHODS. Native vitreal humor was collected during elective pars plana vitrectomy for the treatment of macular pathologies (group 1: ERM; group 2: MH) from patients without any other ocular or systemic disease. The concentrations of 43 chemokines and cytokines were measured in parallel by multiplex beads analysis. Intergroup comparisons were conducted using the Mann-Whitney U test and Bonferroni's correction, at a level of significance of P < 0.0012. RESULTS.Vitreal samples from 31 patients with ERMs (group 1) and from 30 with MHs (group 2) were analyzed. For 12 of the tested cytokines (GM-CSF, MCP-1, MIF, CCL15, CCL20, CCL17, CX3CL1, CXCL10, CXCL16, and TGF-b-1, -2, and -3), no intergroup differences were revealed; for the other 31, the concentrations were higher in the ERM than in the MH group (P < 0.0012 in each case).CONCLUSIONS. The vitreal levels of 72% of the tested cytokines were higher in ERM than in MH. This indicates that even in the absence of clinical markers, activation of inflammatory and profibrotic mechanisms is implicated in the progression of ERMs. Although frequently used as such in the past, eyes with ERMs should be considered with caution as a healthy control group.

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“…IFN-γ alters the antigenicity of RPE cells, activates and recruits leukocytes, and magnifies local inflammatory responses in the outer retina [25,26,27]. Analysis of cytokine levels and macular thickness revealed that IFN-γ was significantly upregulated in patients with thin cystoid macular edema in sarcoidosis [28]. From previous reports, the upregulation of IFN-γ may lead to antiangiogenesis [15].…”

Section: Discussionmentioning

confidence: 99%

Efficient Delivery of siRNA by Atelocollagen in a Murine Laser-Induced Choroidal Neovascularization Model

Ito¹,

Nozaki²,

Sugitani³

et al. 2013

Ophthalmologica

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Purpose: Previous studies have shown that small interfering RNAs (siRNAs) could suppress angiogenesis via stimulation of toll-like receptor-3 (TLR3). The purpose of this study was to determine the efficacy of atelocollagen to deliver siRNA without TLR3 stimulation in the laser-induced choroidal neovascularization (CNV) model. Methods: CNV was induced by laser injury in C57BL/6J mice and volumes were measured 7 days later. Nontargeted siRNA, 21-nucleotide (nt) siRNA-Luc (Luciferase) and 21-nt siRNA-Vegfa were injected into the vitreous following injury. Atelocollagen was incubated with naked 21-nt siRNAs before injection. To block TLR3 endosomal activity, chloroquine was injected intravitreously after laser injury. Results: The mean CNV volumes were significantly smaller in the naked siRNA-Luc, naked siRNA-Vegfa, or siRNA-Vegfa/atelocollagen complex compared with PBS, atelocollagen or siRNA-Luc/atelocollagen complex-injected mice (p < 0.05). Conclusion: These findings demonstrate that atelocollagen may deliver siRNA without nonspecific TLR3 stimulation in the murine laser-CNV model.

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Simultaneous Analysis of Multiple Cytokines in the Vitreous of Patients with Sarcoid Uveitis

Abstract: Patients with ocular sarcoidosis had elevated levels of proinflammatory cytokines in vitreous fluids. Different cytokines might contribute to different stages of macular edema.

Cited by 46 publications

References 34 publications

Association of High-Mobility Group Box-1 With Th Cell–Related Cytokines in the Vitreous of Ocular Sarcoidosis Patients

Association of High-Mobility Group Box-1 With Th Cell–Related Cytokines in the Vitreous of Ocular Sarcoidosis Patients

Vitreal Cytokine Profile Differences Between Eyes With Epiretinal Membranes or Macular Holes

Efficient Delivery of siRNA by Atelocollagen in a Murine Laser-Induced Choroidal Neovascularization Model

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