title: The effects of tenascin C knockdown on trabecular meshwork outflow resistance.
abstract: OBJECTIVE
  Tenascin C (TNC) is a matricellular glycoprotein whose expression in adult tissue is indicative of tissue remodeling. The purpose of the current study was to determine the localization of TNC in trabecular meshwork (TM) tissue and to analyze the effects of TNC on intraocular pressure (IOP).
  
  
  METHODS
  Human TM frontal sections were immunostained with anti-TNC and imaged by confocal microscopy. TNC mRNA and protein levels were quantitated in anterior segments perfused at physiological and elevated pressure. Short, hairpin RNA (shRNA) silencing lentivirus targeting full-length TNC (shTNC) was applied to anterior segment perfusion organ cultures. The IOPs and central corneal thickness (CCT) of wild-type, TNC(-/-), and tenascin X (TNX(-/-)) knockout mice were measured.
  
  
  RESULTS
  TNC was distributed in the juxtacanalicular (JCT) region of adult human TM, predominantly in the basement membrane underlying the inner wall of Schlemm's canal. Application of shTNC lentivirus to human and porcine anterior segments in perfusion culture did not significantly affect outflow rate. Although TNC was upregulated in response to pressure, there was no difference in outflow rate when shTNC-silenced anterior segments were subjected to elevated pressure. Furthermore, IOPs and CCTs were not significantly different between TNC(-/-) or TNX(-/-) and wild-type mice.
  
  
  CONCLUSIONS
  TNC does not appear to contribute directly to outflow resistance. However, TNC immunolocalization in the JCT of adult human eyes suggests that certain areas of the TM are being continuously remodeled with or without an IOP increase.
authors.affiliation: Casey Eye Institute, Oregon Health & Science University, Portland, Oregon 97239, USA. gregorka@ohsu.edu
authors.forename: Kate E
authors.initials: KE
authors.lastname: Keller
authors.forename: Janice A
authors.initials: JA
authors.lastname: Vranka
authors.forename: Ramez I
authors.initials: RI
authors.lastname: Haddadin
authors.forename: Min-Hyung
authors.initials: MH
authors.lastname: Kang
authors.forename: Dong-Jin
authors.initials: DJ
authors.lastname: Oh
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Rhee
authors.forename: Yong-Feng
authors.initials: YF
authors.lastname: Yang
authors.forename: Ying Ying
authors.initials: YY
authors.lastname: Sun
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Kelley
authors.forename: Ted S
authors.initials: TS
authors.lastname: Acott
mesh_terms: D000328:Adult; D000818:Animals; D000869:Anterior Eye Segment / Q000502:physiology; D002102:Cadaver; D002924:Ciliary Body / Q000502:physiology; D005109:Extracellular Matrix / Q000378:metabolism; D020868:Gene Silencing; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D007429:Intraocular Pressure / Q000502:physiology*; D016086:Lentivirus / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009924:Organ Culture Techniques; D015676:Osteonectin / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012590:Sclera / Q000502:physiology; D013552:Swine; D019063:Tenascin / Q000235:genetics* / Q000378:metabolism*; D014129:Trabecular Meshwork / Q000502:physiology*; D014602:Uvea / Q000502:physiology
chemical_list: D015676:Osteonectin; D012333:RNA, Messenger; C577241:SPARC protein, human; D019063:Tenascin
keywords: extracellular matrix; outflow resistance; tenascin C; trabecular meshwork