High interleukin-8 level in aqueous humor is associated with poor prognosis in eyes with open angle glaucoma and neovascular glaucoma

Chono, Ikuyo; Miyazaki, Dai; Miyake, Hitomi; Komatsu, Naoki; Ehara, Fumie; Nagase, Daisuke; Kawamoto, Yukimi; Shimizu, Yumiko; Ideta, Ryuichi; Inoue, Yoshitsugu

doi:10.1038/s41598-018-32725-3

Cited by 57 publications

(51 citation statements)

References 22 publications

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“…An association between IL-8 and ocular disease has been reported in patients with glaucoma, in whom aqueous IL-8 levels were related to faster disease progression. 22 Together, these findings suggest that IL-8 may be an important factor in retinal and optic nerve degeneration, although the cause-effect relationship cannot be elucidated by an observational clinical study. To address this point, a longitudinal study to monitor serum IL-8 levels and their relationships to the functional and structural disease progression will be needed.…”

Section: Discussionmentioning

confidence: 98%

Changes of Serum Inflammatory Molecules and Their Relationships with Visual Function in Retinitis Pigmentosa

Okita

Murakami

Shimokawa

et al. 2020

Invest. Ophthalmol. Vis. Sci.

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Purpose Retinal degeneration involves neuroinflammation, and pro-inflammatory cytokines/chemokines are markedly increased in the eyes of patients with retinitis pigmentosa (RP). In this study, we investigated the changes of serum cytokines/chemokines in RP, and their relationships with visual parameters. Methods Forty-five consecutive patients with typical RP aged 20 to −39 years and 28 age-matched and gender-matched controls were included. Fifteen cytokines (interleukin [IL]-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p70, IL-13, 1L-15, IL-17, IL-23, interferon [IFN]-γ, and tumor necrosis factor [TNF]-α, TNF-β) and 9 chemokines (eotaxin, growth-related oncogene [GRO]-α, I-309, IL-8, IFN-γ-inducible protein [IP]-10, monocyte chemotactic protein [MCP]-1, MCP-2, regulated activation normal T-cell expressed and secreted [RANTES], and thymus and activated regulated chemokine [TARC]) in the serum were simultaneously measured by a multiplexed immunoarray (Q-Plex). Relationships between these cytokines/chemokines and indices of central vision, such as visual acuity (VA), the values of static perimetry tests (Humphrey Field analyzer, the central 10-2 program), and optical coherence tomography measures were analyzed in the patients with RP. Results Among the 15 cytokines and 9 chemokines, serum IL-8 and RANTES levels were significantly increased in patients with RP compared with controls (IL-8: P < 0.0001; RANTES: P < 0.0001). Among the elevated cytokines/chemokines, the levels of IL-8 were negatively correlated with VA (ρ = 0.3596 and P = 0.0165), and the average retinal sensitivity of four central points (ρ = −0.3691 and P = 0.0291), and 12 central points ( ρ = −0.3491 and P = 0.0398), as well as the central subfield thickness ( ρ = −0.3961 and P = 0.0094), and ellipsoid zone width ( ρ = −0.3841 and P = 0.0120). Conclusions Peripheral inflammatory response may be activated and serum IL-8 levels are associated with central vision in patients with RP.

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Section: Discussionmentioning

confidence: 98%

Changes of Serum Inflammatory Molecules and Their Relationships with Visual Function in Retinitis Pigmentosa

Okita

Murakami

Shimokawa

et al. 2020

Invest. Ophthalmol. Vis. Sci.

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“…For example, in glaucoma, a number of studies demonstrate elevated amounts of fibronectin [57][58][59][60][61][62] and connective tissue growth factor 63,64 in the TM. In addition, elevated levels of profibrotic cytokines 27,[65][66][67][68][69] have been reported in the aqueous humor of glaucomatous patients. It is thus inevitable that resident TM cells are continuously subjected to both secreted factors within the tissue and those circulating and passing through the TM.…”

Section: Discussionmentioning

confidence: 99%

Glucocorticoid-induced cell-derived matrix modulates transforming growth factor β2 signaling in human trabecular meshwork cells

Yemanyi

Vranka

Raghunathan

2020

Sci Rep

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Aberrant remodeling of trabecular meshwork (TM) extracellular matrix (ECM) may induce ocular hypertensive phenotypes in human TM (hTM) cells to cause ocular hypertension, via a yet unknown mechanism. Here, we show that, in the absence of exogenous transforming growth factor-beta2 (TGFβ2), compared with control matrices (VehMs), glucocorticoid-induced cell-derived matrices (GIMs) trigger non-Smad TGFβ2 signaling in hTM cells, correlated with overexpression/activity of structural ECM genes (fibronectin, collagen IV, collagen VI, myocilin), matricellular genes (connective tissue growth factor [CTGF], secreted protein, acidic and rich in cysteine), crosslinking genes/enzymes (lysyl oxidase, lysyl oxidase-like 2–4, tissue transglutaminase-2), and ECM turnover genes/enzymes (matrix metalloproteinases-MMP2,14 and their inhibitors-TIMP2). However, in the presence of exogenous TGFβ2, VehMs and GIMs activate Smad and non-Smad TGFβ2 signaling in hTM cells, associated with overexpression of α-smooth muscle actin (α-SMA), and differential upregulation of aforementioned ECM genes/proteins with new ones emerging (collagen-I, thrombospondin-I, plasminogen activator inhibitor, MMP1, 9, ADAMTS4, TIMP1); with GIM-TGFβ2-induced changes being mostly more pronounced. This suggests dual glaucomatous insults potentiate profibrotic signaling/phenotypes. Lastly, we demonstrate type I TGFβ receptor kinase inhibition abrogates VehM-/GIM- and/or TGFβ2-induced upregulation of α-SMA and CTGF. Collectively, pathological TM microenvironments are sufficient to elicit adverse cellular responses that may be ameliorated by targeting TGFβ2 pathway.

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“…Inflammation is a crucial stage of the wound healing process, necessary to attract leukocytes to the wound site to remove debris and pathogens and to trigger the subsequent proliferative stage. Excessive inflammation can lead to fibrotic pathology; however an increase in pro-inflammatory cytokines was associated with poor prognosis following glaucoma filtration surgery 31 . The factors underlying the increased inflammation in these individuals is unclear; there was no difference in baseline clinical inflammation grade between those that did and did not develop ECA.…”

Section: Discussionmentioning

confidence: 99%

The conjunctival transcriptome in Ethiopians after trichiasis surgery: associations with the development of eyelid contour abnormalities and the effect of oral doxycycline treatment

Derrick¹,

Habtamu²,

Tadesse³

et al. 2019

Wellcome Open Res

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Background: Surgery to correct trichiasis is a key component of the World Health Organisation trachoma control strategy, however unfavourable outcomes such as eyelid contour abnormalities (ECA) following surgery are relatively common. This study aimed to understand the transcriptional changes associated with the early development of ECA and the impact of doxycycline, which has anti-inflammatory and anti-fibrotic properties, upon these transcription patterns. Methods: One thousand Ethiopians undergoing trichiasis surgery were enrolled in a randomised controlled trial following informed consent. Equal groups of randomly assigned individuals were orally administered with 100mg/day of doxycycline (n=499) or placebo (n=501) for 28 days. Conjunctival swabs were collected immediately prior to surgery and at one- and six-months post-surgery. 3’ mRNA sequencing was performed on paired baseline and one-month samples from 48 individuals; 12 in each treatment/ECA outcome group. qPCR validation was then performed for 46 genes of interest in 145 individuals who developed ECA at one month and 145 matched controls, using samples from baseline, one and six months. Results: All treatment/outcome groups upregulated genes associated with wound healing pathways at one month relative to baseline, however no individual differences were detected between groups. The summed expression of a highly coexpressed cluster of pro-fibrotic genes was higher in patients that developed ECA in the placebo group relative to controls. qPCR validation revealed that all genes in this cluster and a number of other pro-inflammatory genes were strongly associated with ECA, however these associations were not modulated by trial arm. Conclusions: The development of post-operative ECA is associated with overexpression of pro-inflammatory and pro-fibrotic genes including growth factors, matrix metalloproteinases, collagens and extracellular matrix proteins. There was no evidence that doxycycline modulated the association between gene expression and ECA.

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High interleukin-8 level in aqueous humor is associated with poor prognosis in eyes with open angle glaucoma and neovascular glaucoma

Cited by 57 publications

References 22 publications

Changes of Serum Inflammatory Molecules and Their Relationships with Visual Function in Retinitis Pigmentosa

Changes of Serum Inflammatory Molecules and Their Relationships with Visual Function in Retinitis Pigmentosa

Glucocorticoid-induced cell-derived matrix modulates transforming growth factor β2 signaling in human trabecular meshwork cells

The conjunctival transcriptome in Ethiopians after trichiasis surgery: associations with the development of eyelid contour abnormalities and the effect of oral doxycycline treatment

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