Observation of Schlemm's canal and transluminal trabeculotomy using an ophthalmic endoscope: a case report.

BACKGROUND: Gonioscopy-assisted transluminal trabeculectomy is a novel and useful technique for ab interno trabeculotomy. However, gonioscopy-assisted transluminal trabeculectomy is difficult to perform in patients with corneal opacity or in patients with sequelae of cerebral infarction and cervical osteoarthritis with severe limitation of spinal mobility. This is because observing Schlemm's canal during surgery using gonioscopy is difficult. In this report, we introduce a new and beneficial surgical technique of transluminal trabeculotomy for these patients, using an ophthalmic endoscope for cases in which normal gonioscopy-assisted transluminal trabeculectomy is difficult. CASE PRESENTATION: Our patient was a 65-year-old Japanese man with cervical osteoarthritis with severe limitation of spinal mobility who showed primary open-angle glaucoma of the right eye. He had limited conversion of his head during surgery because of complications. Therefore, we performed transluminal trabeculotomy using an ophthalmic endoscope. Finally, ab interno trabeculotomy of 200 degrees was achieved by this method, and an average reduction in ocular pressure of 60% from baseline was achieved after surgery, with no major complications. CONCLUSIONS: This surgical technique may be useful as an alternative method for normal gonioscopy-assisted transluminal trabeculectomy in difficult cases.

Mesenchymal cells and fluid flow stimulation synergistically regulate the kinetics of corneal epithelial cells at the air-liquid interface.

PURPOSE: In vivo microenvironments are critical to tissue homeostasis and wound healing, and the cornea is regulated by a specific microenvironment complex that consists of cell-cell interactions, air-liquid interfaces, and fluid flow stimulation. In this study, we aimed to clarify the effects of and the correlations among these three component factors on the cell kinetics of corneal epithelial cells. METHODS: Human corneal epithelial-transformed (HCE-T) cells were cocultured with either primary rat corneal fibroblasts or NIH 3T3 fibroblasts. We employed a double-dish culture method to create an air-liquid interface and a gyratory shaker to create fluid flow stimulation. Morphometric and protein expression analyses were performed for the HCE-T cells. RESULTS: Both the primary rat fibroblasts and the NIH 3T3 cells promoted HCE-T cell proliferation, and the presence of fluid flow synergistically enhanced this effect and inhibited the apoptosis of HCE-T cells. Moreover, fluid flow enhanced the emergence of myofibroblasts when cocultured with primary rat fibroblasts or NIH 3T3 cells. Extracellular signal-regulated kinase and p38 signaling were regulated either synergistically or independently by both fluid flow and cellular interaction between the HCE-T and NIH 3T3 cells. CONCLUSION: The cell-cell interaction and fluid flow stimulation in the air-liquid interface synergistically or independently regulated the behavior of HCE-T cells. Fluid flow accelerated the phenotypic change from corneal fibroblasts and NIH 3T3 cells to myofibroblasts. Elucidation of the multicomponent interplay in this microenvironment will be critical to the homeostasis and regeneration of the cornea and other ocular tissues.

Identification of pendrin as a common mediator for mucus production in bronchial asthma and chronic obstructive pulmonary disease.

Excessive production of airway mucus is a cardinal feature of bronchial asthma and chronic obstructive pulmonary disease (COPD) and contributes to morbidity and mortality in these diseases. IL-13, a Th2-type cytokine, is a central mediator in the pathogenesis of bronchial asthma, including mucus overproduction. Using a genome-wide search for genes induced in airway epithelial cells in response to IL-13, we identified pendrin encoded by the SLC26A4 (PDS) gene as a molecule responsible for airway mucus production. In both asthma and COPD mouse models, pendrin was up-regulated at the apical side of airway epithelial cells in association with mucus overproduction. Pendrin induced expression of MUC5AC, a major product of mucus in asthma and COPD, in airway epithelial cells. Finally, the enforced expression of pendrin in airway epithelial cells in vivo, using a Sendai virus vector, rapidly induced mucus overproduction in the lumens of the lungs together with neutrophilic infiltration in mice. These findings collectively suggest that pendrin can induce mucus production in airway epithelial cells and may be a therapeutic target candidate for bronchial asthma and COPD.

Inhibitory mechanism of a cross-class serpin, the squamous cell carcinoma antigen 1.

The squamous cell carcinoma antigen (SCCA) 1 and its homologous molecule, SCCA2, belong to the ovalbumin-serpin family. Although SCCA2 inhibits serine proteinases such as cathepsin G and mast cell chymase, SCCA1 targets cysteine proteinases such as cathepsin S, K, L, and papain. SCCA1 is therefore called a cross-class serpin. The inhibitory mechanism of the standard serpins is well characterized; those use a suicide substrate-like inhibitory mechanism during which an acyl-enzyme intermediate by a covalent bond is formed, and this complex is stable against hydrolysis. However, the inhibitory mechanism of cross-class serpins remains unresolved. In this article, we analyzed the inhibitory mechanism of SCCA1 on a cysteine proteinase, papain. SCCA1 interacted with papain at its reactive site loop, which was then cleaved, as the standard serpins. However, gel-filtration analyses showed that SCCA1 did not form a covalent complex with papain, in contrast to other serpins. Interaction with SCCA1 severely impaired the proteinase activity of papain, probably by inducing conformational change. The decreased, but still existing, proteinase activity of papain was completely inhibited by SCCA1 according to the suicide substrate-like inhibitory mechanism; however, papain recovered its proteinase activity with the compromised level, when all of intact SCCA1 was cleaved. These results suggest that the inhibitory mechanism of SCCA1 is unique among the serpin superfamily in that SCCA1 performs its inhibitory activity in two ways, contributing the suicide substrate-like mechanism without formation of a covalent complex and causing irreversible impairment of the catalytic activity of a proteinase.