Human trabecular meshwork cells as a thyroid hormone target tissue: Presence of functional thyroid hormone receptors

Keith G. Duncan, Michele D. Jumper, Ralff C.J. Ribeiro, Kathy R. Bailey, Paul M. Yen, Akira Sugawara, Ashmi Patel, Robert Stern, William W. Chin, John D. Baxter, Daniel M. Schwartz

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

Purpose: To determine whether human trabecular meshwork cells (HTM) are a potential target tissue for thyroid hormone (3,3',5-triiodothyronine, T3). Methods: Cultured HTM were assayed for the presence of thyroid hormone receptors (TRs) and retinoid X receptors (RXRs) by reverse-transcriptase polymerase chain reaction (RT-PCR) to detected TR and RXR mRNA, and by immunohistochemistry to detect nuclear TR and RXR proteins. Functionality of the TR was determined by analysis of 125I-T3 binding affinity and capacity in HTM nuclear extracts. Effects of T3 on modulation of hyaluronic acid (HA) levels in HTM were measured as a function of dose and duration of T3 administration. Results: Analysis of RT-PCR and immunohistochemistry demonstrated that cultured HTM expressed TRα1, TRα2, and TRβ1 but not TRβ2; and RXRα but not RXRβ and RXRγ isoforms. Saturation binding and analysis of 125I-T3 to HTM nuclear extracts revealed K(d) of 57 pM. The number of T3 binding sites extrapolated from a Scatchard plot was 7.3 x 1010/μg of HTM nuclear protein extract. T3 supplementation reduced the concentration of HA in the cell medium by 32-43% compared to cells grown in the absence of T3. Conclusions: Cultured HTM express three TR isoforms and one RXR isoform, bind T3 with an affinity similar to that of TR in responsive cells, and modulate their HA production in response to T3. These findings indicate that the human trabecular meshwork tissue has the capacity to respond to thyroid hormones.

Original languageEnglish
Pages (from-to)231-240
Number of pages10
JournalGraefe's Archive for Clinical and Experimental Ophthalmology
Volume237
Issue number3
DOIs
Publication statusPublished - 1999 Mar
Externally publishedYes

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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