PMID- 23882691 OWN - NLM STAT- MEDLINE DCOM- 20131031 LR - 20211021 IS - 1552-5783 (Electronic) IS - 0146-0404 (Print) IS - 0146-0404 (Linking) VI - 54 IP - 8 DP - 2013 Aug 19 TI - The effects of tenascin C knockdown on trabecular meshwork outflow resistance. PG - 5613-23 LID - 10.1167/iovs.13-11620 [doi] AB - 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. FAU - Keller, Kate E AU - Keller KE AD - Casey Eye Institute, Oregon Health & Science University, Portland, Oregon 97239, USA. gregorka@ohsu.edu FAU - Vranka, Janice A AU - Vranka JA FAU - Haddadin, Ramez I AU - Haddadin RI FAU - Kang, Min-Hyung AU - Kang MH FAU - Oh, Dong-Jin AU - Oh DJ FAU - Rhee, Douglas J AU - Rhee DJ FAU - Yang, Yong-Feng AU - Yang YF FAU - Sun, Ying Ying AU - Sun YY FAU - Kelley, Mary J AU - Kelley MJ FAU - Acott, Ted S AU - Acott TS LA - eng GR - EY010572/EY/NEI NIH HHS/United States GR - EY003279/EY/NEI NIH HHS/United States GR - EY019654/EY/NEI NIH HHS/United States GR - R01 EY003279/EY/NEI NIH HHS/United States GR - R01 EY019654/EY/NEI NIH HHS/United States GR - R01 EY019643/EY/NEI NIH HHS/United States GR - EY008247/EY/NEI NIH HHS/United States GR - R01 EY008247/EY/NEI NIH HHS/United States GR - R01 EY021800/EY/NEI NIH HHS/United States GR - P30 EY010572/EY/NEI NIH HHS/United States GR - EY019643/EY/NEI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20130819 PL - United States TA - Invest Ophthalmol Vis Sci JT - Investigative ophthalmology & visual science JID - 7703701 RN - 0 (Osteonectin) RN - 0 (RNA, Messenger) RN - 0 (SPARC protein, human) RN - 0 (Tenascin) SB - IM MH - Adult MH - Animals MH - Anterior Eye Segment/physiology MH - Cadaver MH - Ciliary Body/physiology MH - Extracellular Matrix/metabolism MH - Gene Silencing MH - Homeostasis/physiology MH - Humans MH - Intraocular Pressure/*physiology MH - Lentivirus/genetics MH - Mice MH - Mice, Knockout MH - Organ Culture Techniques MH - Osteonectin/genetics/metabolism MH - RNA, Messenger/metabolism MH - Sclera/physiology MH - Swine MH - Tenascin/*genetics/*metabolism MH - Trabecular Meshwork/*physiology MH - Uvea/physiology PMC - PMC3747717 OTO - NOTNLM OT - extracellular matrix OT - outflow resistance OT - tenascin C OT - trabecular meshwork EDAT- 2013/07/25 06:00 MHDA- 2013/11/01 06:00 PMCR- 2013/08/01 CRDT- 2013/07/25 06:00 PHST- 2013/07/25 06:00 [entrez] PHST- 2013/07/25 06:00 [pubmed] PHST- 2013/11/01 06:00 [medline] PHST- 2013/08/01 00:00 [pmc-release] AID - iovs.13-11620 [pii] AID - 10.1167/iovs.13-11620 [doi] PST - epublish SO - Invest Ophthalmol Vis Sci. 2013 Aug 19;54(8):5613-23. doi: 10.1167/iovs.13-11620.