title: Expression and localization of tenomodulin, a transmembrane type chondromodulin-I-related angiogenesis inhibitor, in mouse eyes.
abstract: OBJECTIVE
  To explore the role in the eye of tenomodulin (TeM), a chondromodulin (ChM)-I-related glycoprotein, the expression, localization, and antiangiogenic potential of TeM were investigated.
  
  
  METHODS
  Gene expression and protein localization of TeM in mouse eyes were examined by Northern blot analysis, in situ hybridization, and immunohistochemical analysis. Antiangiogenic function included in the C terminus of TeM and ChM-I was examined in vascular endothelial cells through adenoviral gene transduction.
  
  
  RESULTS
  TeM expression was detectable from day 15 of the embryonic stage and was clearly present in the eye and skin. In situ hybridization of the eye tissues revealed TeM mRNA in the tendon of the extraocular muscle, the sclerocornea, the lens fiber cells, and the ganglion cell layer, inner nuclear layer cells, and pigment epithelium of the retina. Corresponding immunoreactivity of TeM was present in most of these cells. Western blot detected 40- and 45-kDa immunoreactive bands of TeM in the eye as differently glycosylated forms of the transmembrane protein. Production of a secreted form of TeM and ChM-I through adenoviral gene transfer caused effective autocrine suppression of cell proliferation and capillary-like morphogenesis of retina vascular endothelial cells. The condition media from soluble TeM- and ChM-I-overexpressing cells also showed a marked inhibitory effect on in vitro angiogenesis.
  
  
  CONCLUSIONS
  These results indicate a potential role for TeM in prevention of vascular invasion in the mouse eye and the possibility of both TeM and ChM-I as candidates for use in gene therapy approaches to treatment of ocular angiogenesis.
authors.affiliation: Department of Ophthalmology and Visual Science, Osaka University Medical School, Osaka, Japan. oshima@ophthal.med.osaka-u.ac.jp
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Oshima
authors.forename: Chisa
authors.initials: C
authors.lastname: Shukunami
authors.forename: Junichi
authors.initials: J
authors.lastname: Honda
authors.forename: Koji
authors.initials: K
authors.lastname: Nishida
authors.forename: Fumi
authors.initials: F
authors.lastname: Tashiro
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Miyazaki
authors.forename: Yuji
authors.initials: Y
authors.lastname: Hiraki
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Tano
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D020533:Angiogenesis Inhibitors / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002196:Capillaries; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005123:Eye / Q000378:metabolism*; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D008565:Membrane Proteins; D051379:Mice; D009024:Morphogenesis / Q000187:drug effects; D018919:Neovascularization, Physiologic / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000378:metabolism; D014162:Transfection
chemical_list: D020533:Angiogenesis Inhibitors; C489408:Cnmd protein, mouse; D005136:Eye Proteins; D036341:Intercellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D012333:RNA, Messenger; C422444:TNMD protein, human; C486026:Tnmd protein, mouse; C068675:CNMD protein, human