Thyroid Hormone Signaling and Cone Photoreceptor Viability

Thyroid hormone (TH) signaling regulates cell proliferation, differentiation, and apoptosis. In the retina, TH signaling plays a central role in cone opsin expression. TH signaling inhibits S opsin expression, stimulates M opsin expression, and promotes dorsal-ventral opsin patterning. TH signaling has also been associated with cone photoreceptor viability. Treatment with thyroid hormone triiodothyronine (T3) or induction of high T3 by deleting the hormone-inactivating enzyme type 3 iodothyronine deiodinase (DIO3) causes cone death in mice. This effect is reversed by deletion of the TH receptor (TR) gene. Consistent with the T3 treatment effect, suppressing TH signaling preserves cones in mouse models of retinal degeneration. The regulation of cone survival by TH signaling appears to be independent of its regulatory role in cone opsin expression. The mechanism by which TH signaling regulates cone viability remains to be identified. The current understanding of TH signaling regulation in photoreceptor viability suggests that suppressing TH signaling locally in the retina may represent a novel strategy for retinal degeneration management.