Association between corneal endothelial cell densities and elevated cytokine levels in the aqueous humor

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

doi:10.1038/s41598-017-14131-3

Cited by 43 publications

(30 citation statements)

References 41 publications

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“…Further, electron microscopy revealed that CEnCs in bullous keratopathy exhibited serious mitochondrial stress with severe loss of cristae and abnormal vacuolization. Recently, we showed that preoperative cytokine levels in AqH were correlated with CECD after corneal transplantation (8)(9)(10)(11), suggesting that the pathological microenvironment in AqH induces CEnC apoptosis. However, the exact mechanism remains elusive.…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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“…ICAM-1 mediates the recruitment of immune cells to sites of inflammation, 44 and its soluble form, sICAM-1 has been shown to be increased in the AqH of patients with bullous keratopathy. 20,45 Richer et al 44 reported strong correlations between sICAM-1 and soluble apoptotic factors, such as soluble Fas and Fas ligand in rhegmatogenous retinal detachment. Recently, Dohlman et al 46 found that blockade of Eselectin suppressed graft rejection in murine corneal transplantation model, whereas both levels of E-selectin and Pselectin were upregulated in the rejected graft.…”

Section: Discussionmentioning

confidence: 99%

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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“…The suggested causes of endotheliopathy include penetration of PEX material towards the Descemet's membrane [28,29] and changes in the blood-aqueous barrier [30,31]. whereas the PEX group was significantly worse than the FECD group at 3 and 6 months (p=0.062 and 0.008, respectively; Mann-Whitney U test).…”

Section: Discussionmentioning

confidence: 99%

Descemet’s Membrane Endothelial Keratoplasty for Pseudoexfoliation Syndrome: A Case Series

Tase¹,

Shimizu

Hayashi

et al. 2019

Preprint

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Background: To evaluate the clinical outcomes and features of Descemet’s membrane endothelial keratoplasty (DMEK) for eyes with pseudoexfoliation syndrome (PEX). Methods: In this retrospective study, 37 DMEK cases were reviewed from available medical records. Patients who exhibited endothelial dysfunction derived from PEX or Fuchs’ endothelial corneal dystrophy (FECD) and successfully underwent cataract surgery approximately four weeks before DMEK were enrolled. The best spectacle-corrected visual acuity (BSCVA), central corneal thickness (CCT), endothelial cell density (ECD), and incidence of intra-operative/post-operative complications of DMEK were analyzed. Results: This study included 14 eyes of 14 patients (PEX: n=6, FECD: n=8). There was no primary graft failure. In the PEX group, BSCVA improved from 0.67 ± 0.28 preoperatively to 0.43 ± 0.14 at 1 month, 0.27 ± 0.10 at 3 months, and 0.19 ± 0.08 at 6 months after DMEK. The donor corneal ECD was 2,704 ± 225 cells/mm2 preoperatively and decreased to 1,691 ± 498 cells/mm2 at 1 month, 1,425 ± 366 cells/mm2 at 3 months, and 1,281 ± 340 cells/mm2 (52.7 ± 11.7% less than ECD of the donor graft) at 6 months after DMEK. None of the patients required rebubbling. When compared with the FECD group, no statistical difference was observed in CCT (p=0.821); BSCVA (p=0.001) and the reduction rate of ECD (p=0.010) were comparatively worse. Conclusions: DMEK is effective for the treatment of endothelial dysfunction due to PEX.

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Association between corneal endothelial cell densities and elevated cytokine levels in the aqueous humor

Cited by 43 publications

References 41 publications

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

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

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

Descemet’s Membrane Endothelial Keratoplasty for Pseudoexfoliation Syndrome: A Case Series

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