Characteristic Profiles of Inflammatory Cytokines in the Aqueous Humor of Glaucomatous Eyes

Kokubun, Taiki; Tsuda, S.; Kunikata, Hiroshi; Yasuda, Masayuki; Himori, Noriko; Kunimatsu-Sanuki, Shiho; Maruyama, Kouichi; Nakazawa, Toru

doi:10.1080/09273948.2017.1327605

Cited by 57 publications

(67 citation statements)

References 48 publications

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“…10,11,18 However, in line with studies performed by others, 10,19 our results did not show any statistically significant difference in terms of AH Aβ 42 concentration between the glaucoma and control groups or with respect to other clinical parameters. Conversely, we found a significant increase of TP in the AH of glaucomatous patients, consistent with previous reports showing an increment of proinflammatory cytokine [20][21][22][23] and proteins related to the extracellular matrix remodeling 24 in the AH of subjects affected by glaucoma. Interestingly, our results indicate that this increase in TP was greater within the female group of glaucomatous patients, although the lower number of male patients could have biased these results (12 male vs. 20 female glaucomatous AH samples).…”

Section: Discussionsupporting

confidence: 92%

Evaluating the Correlation between Alzheimer's Amyloid-β Peptides and Glaucoma in Human Aqueous Humor

Cappelli

Caudano

Marenco

et al. 2020

Trans. Vis. Sci. Tech.

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Citation: Cappelli F, Caudano F, Marenco M, Testa V, Masala A, Sindaco D, Macrì A, Traverso CE, Iester M, Ricciarelli R. Evaluating the correlation between Alzheimer's amyloid-β peptides and glaucoma in human aqueous humor. Trans Vis Sci Tech. 2020;9(5):21, https://doi.org/10.1167/tvst.9.5.21Purpose: Recent studies suggest that glaucoma may share common pathogenic mechanisms with Alzheimer's disease. To test this hypothesis, we investigated the correlation between glaucoma and amyloid-β 42 (Aβ 42 ) concentration in human samples of aqueous humor (AH).Methods: Eighty-one candidates for cataract or glaucoma surgery were consecutively enrolled, with a median age of 77 years; of these, 32 subjects were affected by glaucoma and 49 were controls. Before surgery, each patient received an ophthalmological examination including biometry, intraocular pressure (IOP) measurement, fundus photography, and determination of the mean thickness of the ganglion cell complex (GCC) and/or retinal nerve fiber layer. During the surgical procedure, an AH sample was collected and immediately processed for total protein (TP) and Aβ 42 evaluation.Results: Aβ 42 levels were not statistically different between the glaucomatous and control samples, but a significant increase in TP concentration was found in the AH of glaucoma patients compared with controls (P = 0.02). In addition, positive correlations were observed between TP and Aβ 42 (r = 0.51; P < 0.0001), between TP and IOP (r = 0.44; P < 0.0001), and between Aβ 42 and IOP (r = 0.22; P = 0.033). Conclusions:Our results indicate that an increased protein concentration in the AH could play a role in the pathogenesis of glaucomatous disease.Translational Relevance: This study strongly supports the hypothesis that increased TP in the AH may have a pathogenic role in glaucoma. Further investigations are needed to clarify whether the protein enhancement represents a causative factor and whether it can be used as a marker of disease or as a novel therapeutic target.

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Section: Discussionsupporting

confidence: 92%

Evaluating the Correlation between Alzheimer's Amyloid-β Peptides and Glaucoma in Human Aqueous Humor

Cappelli

Caudano

Marenco

et al. 2020

Trans. Vis. Sci. Tech.

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“…; Kokubun et al. ) As a consequence of this correlation, all of our results are adjusted for the age of patients. However, systematic corrections for age have not been performed in previous studies, which may have affected the interpretation of these findings.…”

Section: Discussionmentioning

confidence: 97%

“…; Kokubun et al. ) IL‐8 is a main chemoattractant for neutrophils which have been found to accumulate in the trabecular meshwork in POAG. (Taurone et al.…”

Section: Discussionmentioning

confidence: 99%

Intraocular cytokine profile and autoimmune reactions in retinitis pigmentosa, age‐related macular degeneration, glaucoma and cataract

Berge

Fazil

Born

et al. 2018

Acta Ophthalmologica

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Purpose To analyse intraocular cytokine levels and prevalence of intraocular antiretinal antibodies (ARAs) in patients with retinitis pigmentosa (RP), age‐related macular degeneration (AMD), glaucoma and cataract, and correlate the results to clinical manifestations. Methods We collected intraocular fluid samples from patients with RP (n = 25), AMD (n = 12), glaucoma (n = 28) and cataract (n = 22), and serum samples paired with the intraocular fluids from patients with RP (N = 7) and cataract (n = 10). Interleukin (IL)‐1β, IL‐1ra, IL‐2, IL‐6, IL‐6rα, IL‐7, IL‐8, IL‐10, IL‐17A, IL‐23, thymus‐ and activation‐regulated chemokine (TARC), monocyte chemoattractant protein‐1 (MCP‐1), tumour necrosis factor‐alpha (TNF‐α), placental growth factor (PlGF) and vascular endothelial growth factor (VEGF) were measured using a multiplex assay. Antiretinal antibodies (ARA) detection was performed by indirect immunofluorescence. Results Increasing age was associated with increasing levels of IL‐6, IL‐8, TNF‐α and VEGF. All patient groups exhibited distinct profiles of intraocular cytokines. Intraocular levels of IL‐8 were highest in patients with AMD and glaucoma. Cataract patients exhibited high intraocular levels of IL‐23. Intraocular levels of IL‐2, IL‐6, MCP‐1 and PlGF in RP patients exceeded the levels of serum, indicating intraocular production. Intraocular ARAs were found in only one patient with AMD. Conclusion Increased levels of inflammatory cytokines in intraocular fluid of patients with originally noninflammatory ocular diseases show that intraocular inflammation is involved in their pathogenesis of these entities. Moreover, we show that increasing age is associated with increasing levels of intraocular cytokines and conclude that future studies on intraocular mediators should be corrected for age of patients.

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“…MCP-1(CCL2), MIP-1α (CCL3), and MIP-1β (CCL4) act as typical chemoattractant that is involved in the inflammatory reaction by recruiting different immune cells to the injured area (41,42). Additionally, they were previously reported to be increased in many pathological conditions of ocular inflammation, including glaucoma (43) and polypoidal choroidal vasculopathy (PCV) (44). Interestingly, in the present study, we found decreased MCP-1, MIP-1α, and MIP-1β concentrations in the eyes of SG patients when compared with the cataract eyes, indicating a conceivable 'atypical inflammation' in the aqueous humor during the disease progression.…”

Section: Iop Intraocular Pressure; C/d Cup-to-disc Ratio; the Corrementioning

confidence: 99%

Characteristic Cytokine Profiles of Aqueous Humor in Glaucoma Secondary to Sturge-Weber Syndrome

Peng

Ding

et al. 2020

Front. Immunol.

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Patients with Sturge-Weber syndrome (SWS) are susceptible to ocular complications, and among them, glaucoma is one of the most frequent forms. In current study, we utilized multiplex human cytokine antibody array to simultaneously measure the concentration of 40 cytokines in aqueous humor (AH) of patients with SWS-induced glaucoma (SG), or from patients with senile cataract as controls. Compared with the control group, levels of interleukin (IL)-12p40, macrophage inflammatory protein (MIP)-1d, tumor necrosis factor-alpha (TNF-a), IL-5, IL-7, interleukin-6 receptor (IL-6R), and B lymphocyte chemoattractant (BLC) in AH were significantly higher in SG group. Samples from SG patients displayed significantly lower levels of MIP-1b, IL-6, MIP-1a, and monocyte chemoattractant protein (MCP)-1 than controls. Further analysis showed that IL-7, MIP-1a, TNF-a were positively correlated with intraocular pressure (IOP) in patients with early-onset SG. Moreover, IL-12p40 was negatively correlated with age in patients with SG. These cytokines may make contributions to the immunopathogenesis or progression of glaucoma in patients with SWS.

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Characteristic Profiles of Inflammatory Cytokines in the Aqueous Humor of Glaucomatous Eyes

Abstract: The detection rates and levels of various cytokines had different patterns in POAG and NVG patients, suggesting distinctive alterations in the microenvironment in different types of glaucoma.

Cited by 57 publications

References 48 publications

Evaluating the Correlation between Alzheimer's Amyloid-β Peptides and Glaucoma in Human Aqueous Humor

Evaluating the Correlation between Alzheimer's Amyloid-β Peptides and Glaucoma in Human Aqueous Humor

Intraocular cytokine profile and autoimmune reactions in retinitis pigmentosa, age‐related macular degeneration, glaucoma and cataract

Characteristic Cytokine Profiles of Aqueous Humor in Glaucoma Secondary to Sturge-Weber Syndrome

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