The Human Fetal Retinal Pigment Epithelium: A Target Tissue for Thyroid Hormones

Thyroid hormone (T 3 ) has previously been shown to regulate visual function in experimental animals and humans. To determine if T 3 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 3 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 125 I-T 3 to RPE cell nuclear extracts was detected, and Scatchard analysis revealed a K d of 110 pM. To determine if RPE cells can respond to T 3 , hyaluronic acid (HA) levels in cell culture media were measured after 2, 4 or 6 days of growth in medium containing 10 –7 M T 3 . T 3 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 –7 M T 3 (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 –7 M T 3 (p < 0.001, t test). The data indicate that human fetal RPE cells are a direct target for thyroid hormones.