Abstract

Thyroid hormone (T<sub>3</sub>) has previously been shown to regulate visual function in experimental animals and humans. To determine if T<sub>3</sub> exerts direct effects on retinal function, cultured human fetal retinal pigment epithelial (RPE) cells were tested for the presence of thyroid hormone receptors (TRs) and T<sub>3</sub> responses. Using TR-isoform-specific reverse-transcriptase polymerase chain reaction techniques, mRNA was detected for α1, α2 and β1 TR isoforms. Immunohistochemistry using a polyclonal antibody that simultaneously recognizes α1, α2 and β1 TRs showed nuclear staining of the fetal RPE. Specific binding of <sup>125</sup>I-T<sub>3</sub> to RPE cell nuclear extracts was detected, and Scatchard analysis revealed a K<sub>d</sub> of 110 pM. To determine if RPE cells can respond to T<sub>3</sub>, hyaluronic acid (HA) levels in cell culture media were measured after 2, 4 or 6 days of growth in medium containing 10<sup>–7</sup> M T<sub>3</sub>. T<sub>3</sub> inhibited accumulation of HA in the cell culture medium of RPE cells. This effect was not evident at 2 days, but at 4 days there was 42.8% less HA in cell culture medium of RPE cells grown in 10<sup>–7</sup> M T<sub>3</sub> (p < 0.01, t test). The effect persisted through 6 days, when there was 46.3% less HA in cell culture medium of RPE cells grown in 10<sup>–7</sup> M T<sub>3</sub> (p < 0.001, t test). The data indicate that human fetal RPE cells are a direct target for thyroid hormones.

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