Preoperative Aqueous Cytokine Levels Are Associated With a Rapid Reduction in Endothelial Cells After Penetrating Keratoplasty

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

doi:10.1016/j.ajo.2017.07.005

Cited by 38 publications

(25 citation statements)

References 23 publications

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“…22 After DSAEK, the preoperative levels of MCP-1, IFN-c, IL-17A, E-selectin, and sICAM-1 were correlated with postoperative ECD in eyes with pseudophakic bullous keratopathy. MCP-1 is the main chemotactic factor for the migration of monocytes/macrophages and the pathogenesis of chronic inflammation.…”

Section: Discussionmentioning

confidence: 88%

“…[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%

“…In our latest study, we showed that higher preoperative aqueous levels of specific cytokines were associated with rapid ECD loss after PKP. 22 The purpose of this study is to evaluate the association between preoperative cytokine levels in the AqH and reduction of ECD following DSAEK.…”

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confidence: 99%

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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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Section: Discussionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

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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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“…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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183

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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“…We performed corneal transplantation, conventional PK, and modern lamellar keratoplasty, Descemet stripping automated endothelial keratoplasty (DSAEK), in a standard fashion as previously described (9)(10)(11)(12). Both after PK and DSAEK, all patients were prescribed the eye drops levofloxacin (Santen, Osaka, Japan) and betamethasone 0.1% eye drops (Santen) for use five times a day.…”

Section: Corneal Transplantation Procedures and Postoperative Managementmentioning

confidence: 99%

Pathological processes in aqueous humor due to iris atrophy predispose to early corneal graft failure in humans and mice

et al. 2020

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Corneal endothelial cell (CEnC) loss after corneal transplantation is the major cause of graft failure and remains a clinically relevant challenge to overcome. Accumulated knowledge derived from long-term clinical outcomes suggested that elevated protein levels in the aqueous humor are associated with CEnC loss. However, the full spectrum of driver proteins and molecular processes remains to be determined. Here, we defined the somatic microenvironmental landscape and cellular response across human aqueous humor in samples with poor corneal transplantation clinical outcomes using multiomics analyses and clarified specific driver alterations, including complement activation and disturbed energy homeostasis. These driver alterations were also confirmed in aqueous humor from a novel murine model that spontaneously develops iris atrophy, leading to CEnC loss. The application of the integrative multiomics performed in human samples to the novel murine model will help the development of therapeutic modalities for patients with CEnC loss after corneal transplantation.

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Preoperative Aqueous Cytokine Levels Are Associated With a Rapid Reduction in Endothelial Cells After Penetrating Keratoplasty

Cited by 38 publications

References 23 publications

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

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

Inflammatory Response in Dry Eye

Pathological processes in aqueous humor due to iris atrophy predispose to early corneal graft failure in humans and mice

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