Overexpression of optineurin E50K disrupts Rab8 interaction and leads to a progressive retinal degeneration in mice

Glaucoma is one of the leading causes of bilateral blindness affecting nearly 8 million people worldwide. Glaucoma is characterized by a progressive loss of retinal ganglion cells (RGCs) and is often associated with elevated intraocular pressure (IOP). However, patients with normal tension glaucoma (NTG), a subtype of primary open-angle glaucoma (POAG), develop the disease without IOP elevation. The molecular pathways leading to the pathology of NTG and POAG are still unclear. Here, we describe the phenotypic characteristics of transgenic mice overexpressing wild-type (Wt) or mutated optineurin (Optn). Mutations E50K, H486R and Optn with a deletion of the first (amino acids 153–174) or second (amino acids 426–461) leucine zipper were used for overexpression. After 16 months, histological abnormalities were exclusively observed in the retina of E50K mutant mice with loss of RGCs and connecting synapses in the peripheral retina leading to a thinning of the nerve fiber layer at the optic nerve head at normal IOP. E50K mice also showed massive apoptosis and degeneration of entire retina, leading to approximately a 28% reduction of the retina thickness. At the molecular level, introduction of the E50K mutation disrupts the interaction between Optn and Rab8 GTPase, a protein involved in the regulation of vesicle transport from Golgi to plasma membrane. Wt Optn and an active GTP-bound form of Rab8 complex were localized at the Golgi complex. These data suggest that alternation of the Optn sequence can initiate significant retinal degeneration in mice

Discovery of Molecular Markers to Discriminate Corneal Endothelial Cells in the Human Body

The corneal endothelium is a monolayer of hexagonal corneal endothelial cells (CECs) on the inner surface of the cornea. CECs are critical in maintaining corneal transparency through their barrier and pump functions. CECs in vivo have a limited capacity in proliferation, and loss of a significant number of CECs results in corneal edema called bullous keratopathy which can lead to severe visual loss. Corneal transplantation is the most effective method to treat corneal endothelial dysfunction, where it suffers from donor shortage. Therefore, regeneration of CECs from other cell types attracts increasing interests, and specific markers of CECs are crucial to identify actual CECs. However, the currently used markers are far from satisfactory because of their non-specific expression in other cell types. Here, we explored molecular markers to discriminate CECs from other cell types in the human body by integrating the published RNA-seq data of CECs and the FANTOM5 atlas representing diverse range of cell types based on expression patterns. We identified five genes, CLRN1, MRGPRX3, HTR1D, GRIP1 and ZP4 as novel markers of CECs, and the specificities of these genes were successfully confirmed by independent experiments at both the RNA and protein levels. Notably none of them have been documented in the context of CEC function. These markers could be useful for the purification of actual CECs, and also available for the evaluation of the products derived from other cell types. Our results demonstrate an effective approach to identify molecular markers for CECs and open the door for the regeneration of CECs in vitro

SURVEY OF INFLUENZA VIRUSES IN FERAL BIRDS IN 1979 AND ISOLATION OF A STRAIN POSSESSING Hav6Nav5 FROM CLOACA OF AN EASTERN DUNLIN

In the course of a survey in 1979 of influenza virus in feral birds, including 255 water fowls of 19 species, 719 small migrating birds of 32 species and 126 sea birds of 6 species, an influenza virus was isolated from a cloacal swab of one of the 38 eastern dunlins (Calidris alpina sakhalina) examined. No influenza virus was isolated from the other birds. The isolate possessed Hav6 hemagglutinin and Nav5 neuraminidase and was designated as A/eastern dunlin/Hokkaido/101/79 (Hav6Nav5)

自家移植歯をブリッジ支台歯に応用した一症例

A case of fixed partial denture with autogenous tooth transplantation is reported in this paper. The maxillary left third molar of a 37-year-old male patient was transplanted in mandibular left second molar position, which had been lost a few years before. The endodontic treatment for the transplanted tooth was extraorally performed in the procedure of transplantation. The distal root of mandibular left first molar was then extracted because of root fracture. A provisional restoration and a ceramometal fixed partial denture were set 1 month and 6 months after transplantation, respectively. No problem was found in the follow-up period of 15 months after transplantation, clinically and radiografically. Clinical efficiency and problem of autogenous tooth transplantation were discussed, and more exact predictability was needed for wider clinical application of this technique