Iris Damage Is Associated With Elevated Cytokine Levels in Aqueous Humor

Aketa, Naohiko; Yamaguchi, Takefumi; Suzuki, Terumasa; Higa, Kazunari; Yagi-Yaguchi, Yukari; Satake, Yoshiyuki; Ohta, Michio; Shimazaki, Jun

doi:10.1167/iovs.17-21421

Cited by 57 publications

(37 citation statements)

References 43 publications

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“…IL-12 inhibits apoptosis of ganglion cells and then protects the optic nerve. IL-4 plays an important role during the process of optic nerve injury, and its high expression represents serious optic nerve injury (21,22). These studies are consistent with our conclusions.…”

Section: Lncrna Malat1 Lncrna Anril ---------------------------------supporting

confidence: 91%

Expression and clinical value of lncRNA MALAT1 and lncRNA ANRIL in glaucoma patients

Zheng

Gao

et al. 2019

Exp Ther Med

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Expression and clinical value of long non-coding RNA (lncRNA) MALAT1 and lncRNA ANRIL in glaucoma patients were investigated. Altogether 86 glaucoma patients who were diagnosed (study group) and 86 people who underwent physical examinations and were confirmed to be healthy (control group) in the Hospital of Chengdu University of Traditional Chinese Medicine from January 2016 to June 2018 were enrolled. Expression of the serum lncRNA MALAT1, lncRNA ANRIL, pigment epithelium-derived factor (PEDF), homocysteine (Hcy), and inflammatory cytokines [interleukin-12 (IL-12), interleukin-4 (IL-4) and interferon-γ (IFN-γ)] was detected. The clinical significance of lncRNA MALAT1 and lncRNA ANRIL was analyzed. Compared with those in the control group, patients in the study group had significantly lower expression of serum lncRNA MALAT1 and lncRNA ANRIL (P<0.05), significantly lower expression of serum PEDF and IL-12 (P<0.05), and significantly higher expression of serum Hcy and IL-4 (P<0.05), without significant difference in the expression of serum IFN-γ between the two groups (P>0.05). Serum lncRNA MALAT1 and lncRNA ANRIL were positively correlated with PEDF and IL-12 (P<0.05), but negatively correlated with Hcy and IL-4 (P<0.05). The diagnostic value of the combined detection of lncRNA MALAT1 and lncRNA ANRIL was higher than that of lncRNA MALAT1 alone and lncRNA ANRIL alone. The expression of lncRNA MALAT1 and lncRNA ANRIL was significantly related to the pathological staging of the patients (P<0.05), not the sex, age, body mass index (BMI), types, and presence or absence of myopia (P>0.05). lncRNA MALAT1 and lncRNA ANRIL are poorly expressed in the serum of glaucoma patients and related to the patients' conditions. Their combined detection has high diagnostic value for the disease. Therefore, they may be used as new molecular targets for the diagnosis and severity evaluation of glaucoma patients.

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Section: Lncrna Malat1 Lncrna Anril ---------------------------------supporting

confidence: 91%

Expression and clinical value of lncRNA MALAT1 and lncRNA ANRIL in glaucoma patients

Zheng

Gao

et al. 2019

Exp Ther Med

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“…20 Moreover, the iris damage was associated with the elevation of aqueous cytokine levels. 21 However, these recent reports were cross-sectional studies and the elevated cytokine levels might just be the results, not the cause, of endothelial cell loss. Thus, we conducted this prospective study to assess the association of preoperative cytokine levels and postoperative ECD after corneal transplantation.…”

Section: Discussionmentioning

confidence: 97%

“…[20][21][22] Therefore, the translational impact of the current study into clinical practice may be poor. Moreover, the current study might have been biased in that patients with severe conditions used steroid eye drops, whereas some of the patients with mild bullous keratopathy did not.…”

Section: Discussionmentioning

confidence: 99%

“…19 We recently showed that inflammatory cytokine levels were elevated in the AqH of eyes with bullous keratopathy and reduced ECDs, 20 and that iris damage was associated with an elevation in aqueous cytokine levels. 21 Collectively, these results suggest that inflammatory factors in the AqH directly influence endothelial cell loss. However, an elevation in aqueous cytokine levels can just be the result, not the direct cause, following endothelial cell loss.…”

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confidence: 85%

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Preoperative Aqueous Cytokine Levels are Associated With Endothelial Cell Loss After Descemet's Stripping Automated Endothelial Keratoplasty

Yazu

Yamaguchi

Aketa

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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Citation: Yazu H, Yamaguchi T, Aketa N, et al. Preoperative aqueous cytokine levels are associated with endothelial cell loss after Descemet's stripping automated endothelial keratoplasty. Invest Ophthalmol Vis Sci. 2018;59:612-620. https://doi.org/ 10.1167/iovs.17-23049 PURPOSE. To evaluate the association between endothelial cell density (ECD) after Descemet's stripping automated endothelial keratoplasty (DSAEK) and preoperative cytokine levels in the aqueous humor (AqH).METHODS. This prospective consecutive case series included 97 consecutive patients who underwent DSAEK (64 eyes) or cataract surgery (33 eyes). AqH samples were collected at the beginning of each surgery. The levels of cytokines (IL-1a, IL-1b, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-17A, IFN-a, IFN-c, monocyte chemotactic protein [MCP]-1, E-selectin, P-selectin, and soluble intercellular adhesion molecule [sICAM]-1) in the AqH were measured by multiplex beads immunoassay. The correlations between preoperative aqueous cytokine levels and the ECD at 12 months after DSAEK were analyzed.RESULTS. The ECD decreased from 2747 6 259 cells/mm 2 in the donor graft to 1235 6 607 cells/mm 2 at 12 months after DSAEK. In all subjects undergoing DSAEK, the postoperative ECD at 12 months was significantly correlated with the preoperative levels of MCP-1 (r ¼ À0.467, 95% confidence interval [CI]: À0.650 to À0.222, P ¼ 0.0003). In an analysis excluding Fuchs endothelial corneal dystrophy (11 eyes), the ECD at 12 months after DSAEK was significantly correlated with preoperative levels of IL-17A (r ¼ À0.635, 95% CI: À0.819 to À0.319, P ¼ 0.0004), MCP-1 (r ¼ À0.605, 95% CI: À0.779 to À0.345, P < 0.0001), IFN-c (r ¼ À0.633, 95% CI: À0.796 to À0.385, P < 0.0001), E-selectin (r ¼ À0.516, 95% CI: À0.756 to À0.276, P ¼ 0.0004), and sICAM-1 (r ¼ À0.537, 95% CI: À0.735 to À0.253, P ¼ 0.0005).CONCLUSIONS. Higher preoperative levels of IL-17A, MCP-1, IFN-c, E-selectin, and sICAM-1 in the AqH were associated with lower ECD after DSAEK for bullous keratopathy.

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“…We recently found elevated levels of aqueous cytokines in chronic ocular surface diseases, which suggests the existence of chronic inflammatory conditions in the anterior chamber, leading to cataract formation or reduction of CECD, if the corneal epithelial barrier function breaks down. 63 Furthermore, we demonstrated a connection among iris pigment damage, elevated cytokine levels in the aqueous humor and CECD in eyes with various ocular conditions, including bullous keratopathy and post-penetrating keratoplasty, [118][119][120][121] providing evidence that a ''chronic inflammatory'' microenvironment in the anterior segment of the eye supports the pathogenesis of these conditions. With chronic inflammation, various changes occur: loss of goblet cells in the conjunctiva, limbal stem cell loss, aqueous tear deficiency, immune cell infiltration into the corneal stroma, decreased CECD, corneal nerve loss and elevated cytokine levels in the tears and aqueous humor.…”

Section: Dry-eye-associated Inflammation and The Corneal Microenvironmentioning

confidence: 99%

Inflammatory Response in Dry Eye

Yamaguchi

2018

Invest. Ophthalmol. Vis. Sci.

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192

120

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PURPOSE. Dry eye is a major ocular pathology worldwide. Although dry eye is a multifactorial disease, recent studies have shown that chronic immunologic processes have a pivotal role in its pathogenesis, characterized by the infiltration of immune cells in the lacrimal glands, elevated levels of tear inflammatory cytokines, and increased density of immune cells in the cornea and conjunctiva. This review describes the recent advances in understanding the relationship between dry eye and inflammation. METHODS. This narrative review is based on searches of recent international literature using terms related to the immune response in dry eye, and includes clinical trials, animal experiments, and expert reviews. RESULTS. Although dry eye presents clinically as tear film instability associated with corneal/ conjunctival epithelial disorders, Meibomian gland dysfunction, and decreased visual function, recent laboratory and clinical studies have indicated inflammation in the lacrimal glands, Meibomian glands, conjunctiva, cornea, and aqueous tears. Furthermore, inflammation at these locations leads to conjunctival goblet cell apoptosis, corneal epithelial barrier disruption, and corneal nerve damage. These inflammatory outcomes can be exacerbated by intrinsic and extrinsic factors, such as aging, sex steroid hormone, autoimmune diseases, contact lens use, visual display terminals, and dry environment. CONCLUSIONS. Recent advances in dry eye research have revealed the inflammatory process and its pathogenesis, which has been proposed as an ''inflammatory vicious cycle'' of dry eye. Comprehensive assessment of dry eye based on inflammation will improve the selection of treatments and help break the inflammatory cycle in clinical settings.

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Iris Damage Is Associated With Elevated Cytokine Levels in Aqueous Humor

Cited by 57 publications

References 43 publications

Expression and clinical value of lncRNA MALAT1 and lncRNA ANRIL in glaucoma patients

Expression and clinical value of lncRNA MALAT1 and lncRNA ANRIL in glaucoma patients

Preoperative Aqueous Cytokine Levels are Associated With Endothelial Cell Loss After Descemet's Stripping Automated Endothelial Keratoplasty

Inflammatory Response in Dry Eye

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