title: Angiopoietin-like 7 secretion is induced by glaucoma stimuli and its concentration is elevated in glaucomatous aqueous humor.
abstract: OBJECTIVE
  To investigate the possibility that Angiopoietin-like 7 (ANGPTL7) protein is involved in the pathogenesis of glaucoma.
  
  
  METHODS
  Primary human trabecular meshwork (TM) cells and corneoscleral explants were stimulated with either dexamethasone (DEX) or transforming growth factor beta (TGFbeta), and ANGPTL7 protein secreted into culture medium was determined by Western blot analysis. The effect of stable overexpression of ANGPTL7 in transfected immortalized TM cell lines on collagen expression was investigated by immunocytochemistry. Localization of ANGPTL7 protein in human eyes was determined by immunohistochemistry. The concentration of ANGPTL7 protein in aqueous humor (AH) from patients with glaucoma and control patients was compared by Western blot analysis. The beagle model of primary open-angle glaucoma (POAG) was used to correlate ANGPTL7 protein levels in canine AH with disease progression.
  
  
  RESULTS
  TGFbeta and DEX stimulated secretion of ANGPTL7 protein by TM cells and corneoscleral explants. Overexpression of ANGPTL7 by immortalized TM cell lines increased expression of type I collagen. Expression of ANGPTL7 protein was located in the corneal stroma, near the limbus, and throughout the sclera, with lower expression in the TM. In the lamina cribrosa, ANGPTL7 expression was associated with the cribriform plates. The concentration of ANGPTL7 protein was elevated in AH from patients with glaucoma and increased as disease progressed in POAG beagle dogs.
  
  
  CONCLUSIONS
  Induction of ANGPTL7 secretion by glaucoma stimuli and increased concentration of ANGPTL7 in glaucomatous AH suggest that ANGPTL7 is overexpressed in glaucoma. Since overexpression of ANGPTL7 increases collagen expression, a potential disease mechanism, ANGPTL7 could have a pathogenic role in glaucoma, and may serve as a potential therapeutic target.
authors.affiliation: Department of Ophthalmology and Visual Sciences, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
authors.forename: John
authors.initials: J
authors.lastname: Kuchtey
authors.forename: Maria E
authors.initials: ME
authors.lastname: Källberg
authors.forename: Kirk N
authors.initials: KN
authors.lastname: Gelatt
authors.forename: Tommy
authors.initials: T
authors.lastname: Rinkoski
authors.forename: András M
authors.initials: AM
authors.lastname: Komàromy
authors.forename: Rachel W
authors.initials: RW
authors.lastname: Kuchtey
mesh_terms: D000091307:Angiopoietin-Like Protein 7; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism*; D015153:Blotting, Western; D002460:Cell Line; D024042:Collagen Type I / Q000378:metabolism; D003315:Cornea / Q000187:drug effects* / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D004283:Dog Diseases / Q000378:metabolism; D004285:Dogs; D019084:Fluorescent Antibody Technique, Indirect; D005902:Glaucoma, Open-Angle / Q000378:metabolism* / Q000662:veterinary; D006801:Humans; D007124:Immunoenzyme Techniques; D012590:Sclera / Q000187:drug effects* / Q000378:metabolism; D014129:Trabecular Meshwork / Q000187:drug effects* / Q000378:metabolism; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
chemical_list: C530622:ANGPTL7 protein, human; D000091307:Angiopoietin-Like Protein 7; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; D024042:Collagen Type I; D016212:Transforming Growth Factor beta; D003907:Dexamethasone