Norimasa Nomi

Two cases of methicillin-resistant Staphylococcus aureus keratitis after Epi-LASIK

BackgroundWe describe two severe cases of methicillin-resistant Staphylococcus aureus (MRSA) keratitis following Epi-LASIK surgery.CasesOne patient was a 23-year-old man who underwent Epi-LASIK surgery in both eyes. He developed an infectious corneal ulcer in one eye 2 days after surgery and was referred to us 7 days post-surgery with corneal perforation, for which we performed therapeutic penetrating keratoplasty. The other patient was a 32-year-old man who developed infectious keratitis in one eye 4 days after bilateral Epi-LASIK and was referred to us 2 days later.ObservationsMicrobial testing revealed MRSA infection as the cause of the keratitis in both patients which was successfully treated with vancomycin eyedrops.ConclusionInfectious keratitis after refractive surgery is uncommon; it is important to diagnose this condition, identify the causative agent, and initiate treatment with appropriate antibiotics as soon as possible.

Upregulation of ZO-1 in cultured human corneal epithelial cells by a peptide (PHSRN) corresponding to the second cell-binding site of fibronectin.

PURPOSE To investigate the effect of a peptide (PHSRN) corresponding to the second cell-binding site of fibronectin on the expression of ZO-1 in cultured human corneal epithelial (HCE) cells. METHODS The effects of the PHSRN peptide on the expression of ZO-1, -2, and -3; claudin; and occludin were determined by reverse transcription-polymerase chain reaction (RT-PCR), immunoblot, and immunofluorescence analyses. Phosphorylation of mitogen-activated protein kinases (MAPKs) and the transcription factor c-Jun was assessed with a multiplex analysis system and immunoblot analysis. The barrier function of cultured HCE cells was evaluated by measurement of transepithelial electrical resistance. RESULTS RT-PCR and immunoblot analyses revealed the PHSRN peptide increased the amounts of ZO-1 mRNA and protein in HCE cells in a concentration- and time-dependent manner. The PHSRN peptide had no effect on the expression of ZO-2, ZO-3, claudin, or occludin. Immunofluorescence microscopy showed that the PHSRN peptide did not affect the localization of ZO-1 at the interfaces of neighboring cells. The PHSRN peptide induced the phosphorylation of the MAPKs ERK, p38, and JNK as well as that of c-Jun. The upregulation of ZO-1 expression by the PHSRN peptide was blocked by inhibitors of signaling by ERK (PD098059), p38 (SB203580), or JNK (JNK inhibitor II). The PHSRN peptide had no effect on the transepithelial electrical resistance of cultured HCE cells. CONCLUSIONS The PHSRN peptide upregulated the expression of ZO-1 through activation of MAPK signaling pathways in HCE cells. This effect of the PHSRN sequence of fibronectin may contribute to the formation of tight junctions and play an important role in the differentiation of corneal epithelial cells.

Release of Interleukins 6 and 8 Induced by Zymosan and Mediated by MAP Kinase and NF-κB Signaling Pathways in Human Corneal Fibroblasts

PURPOSE Zymosan is derived from the cell wall of yeast and induces immune responses associated with fungal infection. The effects of zymosan on the expression of proinflammatory cytokines, chemokines, and adhesion molecules and on the activity of signaling pathways were examined in cultured human corneal fibroblasts. METHODS Release of the proinflammatory cytokines interleukin (IL)-6, IL-1beta, and IL-12 and of the chemokines IL-8, IP-10, and RANTES was measured with enzyme-linked immunosorbent assays. Expression of intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1) was evaluated by immunoblot and immunofluorescence analyses. Phosphorylation of mitogen-activated protein kinases (MAPKs) and the NF-kappaB inhibitory protein IkappaB-alpha was assessed by immunoblot analysis. Subcellular localization of the p65 subunit of the transcription factor NF-kappaB was determined by immunofluorescence analysis. RESULTS Zymosan induced the release of IL-6 and IL-8 from corneal fibroblasts without affecting either the release of IL-1beta, IL-12, IP-10, or RANTES or the expression of ICAM-1 or VCAM-1. Zymosan also activated the MAPKs ERK, p38, and JNK and induced the phosphorylation of IkappaB-alpha and the nuclear translocation of p65 in these cells. The zymosan-induced release of IL-6 and IL-8 was attenuated by inhibitors of ERK, p38, JNK, and NF-kappaB signaling. CONCLUSIONS Zymosan induces the release of IL-6 and IL-8 from human corneal fibroblasts in a manner dependent on MAPK and NF-kappaB signaling pathways. Corneal fibroblasts may thus modulate the local immune response to fungal infection in the corneal stroma.

Immunohistofluorescence analysis of myofibroblast transdifferentiation in human corneas with bullous keratopathy.

Purpose: To detect the transdifferentiation of keratocytes into myofibroblasts in human corneas with bullous keratopathy and to examine the relation of such transdifferentiation to the clinical course of the disease. Methods: Twenty patients with bullous keratopathy who underwent penetrating keratoplasty were enrolled in the study. Corneal buttons collected during surgery were examined for expression of α-smooth muscle actin (αSMA) by immunoblot analysis and by immunofluorescence analysis of whole-mount preparations. The course of bullous keratopathy was evaluated from clinical charts. Results: Immunoblot analysis revealed a marked increase in αSMA expression in some corneas affected by bullous keratopathy. Immunofluorescence analysis revealed that αSMA was expressed in myofibroblastic cells in the stroma of 10 of the 20 corneas examined. Expression of αSMA was detected in subjects with a clinical history of corneal epithelial erosion from 12 months after the onset of clinical stromal edema. In contrast, in subjects without a clinical history of epithelial erosion, αSMA expression was not detected until at least 27 months after the onset of stromal edema. The incidence of αSMA expression in stromal cells was not significantly associated with topical steroid administration. Conclusions: Transdifferentiation of keratocytes into myofibroblasts was observed in human corneas affected by bullous keratopathy. Such transdifferentiation occurred earlier after the onset of stromal edema in patients with a clinical history of epithelial erosion than in those without such a history.

Identification of common secreted factors in human corneal fibroblasts exposed to LPS, poly(I:C), or zymosan.

Infection of the cornea with bacteria, viruses, or fungi can result in corneal ulceration. Corneal stromal cells participate in the immune and inflammatory responses to such infection in part by producing various cytokines and chemokines. The effects of lipopolysaccharide (LPS), polyinosinic-polycytidylic acid [poly(I:C)], and zymosan as surrogates for bacteria, viruses, and fungi, respectively, on the release of cytokines and chemokines from cultured human corneal fibroblasts were examined in order to identify common factors in infectious corneal keratitis. The secretion of various cytokines and chemokines by human corneal fibroblasts exposed to LPS, poly(I:C), or zymosan was measured with a multiplex assay system. LPS induced the release of interleukin (IL)-6, IL-8, MCP-1, RANTES, IP-10, eotaxin, and IL-12 from corneal fibroblasts. Poly(I:C) stimulated the secretion of IL-6, IL-8, MCP-1, RANTES, IP-10, eotaxin, MIP-1β, and interferon-γ, whereas zymosan triggered the production of IL-6, IL-8, and MCP-1. LPS, poly(I:C), and zymosan thus each induced a distinct pattern of cytokine and chemokine release from human corneal fibroblasts, with the release of IL-6, IL-8, and MCP-1 being commonly elicited by all three agents. Our results suggest that IL-6, IL-8, and MCP-1 may therefore play a key role in the inflammatory response to corneal infection.

Combination management by C-arm fluoroscopy and extraocular muscle severance for penetrating ocular trauma with a retrobulbar foreign body.

ABSTRACT We report here the successful removal of a retrobulbar metallic foreign body in a patient with penetrating ocular trauma by a transconjunctival approach and combination management with C-arm fluoroscopy and extraocular muscle severance. A 37-year-old man sustained a penetrating injury to the right eye while using an iron hammer. Initial slitlamp examination revealed a corneoscleral laceration, iridocele, anterior chamber collapse, and a traumatic cataract. Visual acuity in the right eye was limited to the perception of hand motion. Computed tomography revealed an orbital foreign body in the retrobulbar area. The patient underwent corneoscleral suturing, severance of extraocular muscles, removal of the foreign body with guidance by C-arm fluoroscopy, pars plana lensectomy, and pars plana vitrectomy. Combination management with C-arm fluoroscopy and extraocular muscle severance may thus be a suitable approach to the removal of a retrobulbar metallic foreign body.

Nevus depigmentosus with pale skin, yellow-brown hair and a light brown iris.

Nevus depigmentosus is a leukoderma present at birth or with onset early in life [1]. Simultaneous involvement of skin and hair, or of skin and an eye, has previously been reported. Here, we show a nevus depigmentosus involving skin, hair and an eye in a one-year-old Japanese boy.A one-year-old Japanese boy was referred to us with a hypopigmented macule and yellow-brown hair on the left face and scalp. The parents noticed them at birth. A physical examination revealed a hypopigmented lesion with [...]