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 p otential target tissue for thyroid hormone (3,3',5-triiodothyronine, T-3). Methods: Cultured HTM were assayed for the presence of thyroid hormone rece ptors (TRs) and retinoid X receptors (RXRs) by reverse-transcriptase polyme rase chain reaction (RT-PCR) to detected TR and RXR mRNA, and by immunohist ochemistry to detect nuclear TR and RXR proteins. Functionality of the TR w as determined by analysis of I-125-T-3 binding affinity and capacity in HTM nuclear extracts. Effects of T-3 on modulation of hyaluronic acid (HA) lev els in HTM were measured as a function of dose and duration of T-3 administ ration. Results: Analysis of RT-PCR and immunohistochemistry demonstrated that cult ured HTM expressed TR alpha 1, TR alpha 2, and TR beta 1 but not TR beta 2; and RXR alpha but not RXR beta and RXR gamma isoforms. Saturation binding and analysis of I-125-T-3 to HTM nuclear extracts revealed K-d of 57 pM. Th e number of T-3 binding sites extrapolated from a Scatchard plot was 7.3x10 (10)/mu g of HTM nuclear protein extract. T-3 supplementation reduced the c oncentration of HA in the cell medium by 32-43% compared to cells grown in the absence of T-3. Conclusions: Cultured HTM express three TR isoforms and one RXR isoform, bi nd T-3 with an affinity similar to that of TR in responsive cells, and modu late their HA production in response to T-3. These findings indicate that t he human trabecular meshwork tissue has the capacity to respond to thyroid hormones.