The effects of tenascin C knockdown on trabecular meshwork outflow resistance

Kate E. Keller, Janice A. Vranka, Ramez I. Haddadin, Min Hyung Kang, Dong Jin Oh, Douglas J. Rhee, Yong feng Yang, Ying Ying Sun, Mary J. Kelley, Ted S. Acott

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Purpose. 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.

Original languageEnglish (US)
Pages (from-to)5613-5623
Number of pages11
JournalInvestigative Ophthalmology and Visual Science
Volume54
Issue number8
DOIs
StatePublished - Aug 28 2013

Keywords

  • Extracellular matrix
  • Outflow resistance
  • Tenascin C
  • Trabecular meshwork

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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