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

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.