Type 3 deiodinase, a thyroid-hormone-inactivating enzyme, controls survival and maturation of cone photoreceptors

Lily Ng, Arkady Lyubarsky, Sergei S. Nikonov, Michelle Ma, Maya Srinivas, Benjamin Kefas, Donald L. St. Germain, Arturo Hernandez, Edward N Pugh Jr, Douglas Forrest

Research output: Contribution to journalArticle

99 Scopus citations

Abstract

Maturation of the mammalian nervous system requires adequate provision of thyroid hormone and mechanisms that enhance tissue responses to the hormone. Here, we report that the development of cones, the photoreceptors for daylight and color vision, requires protection from thyroid hormone by type 3 deiodinase, a thyroid hormone-inactivating enzyme. Type 3 deiodinase, encoded by Dio3, is expressed in the immature mouse retina. In Dio3-/- mice, ∼80% of cones are lost through neonatal cell death. Cones that express opsin photopigments for response to both short (S) and medium-long (M) wavelength light are lost. Rod photoreceptors, which mediate dim light vision, remain essentially intact. Excessive thyroid hormone in wild-type pups also eliminates cones. Cone loss is mediated by cone-specific thyroid hormone receptor β2 (TRβ2) as deletion of TRβ2 rescues cones in Dio3-/- mice. However, rescued cones respond to short but not longer wavelength light because TRβ2 under moderate hormonal stimulation normally inducesMopsin and controls the patterning ofMand S opsins over the retina. The results suggest that type 3 deiodinase limits hormonal exposure of the cone to levels that safeguard both cone survival and the patterning of opsins that is required for cone function.

Original languageEnglish (US)
Pages (from-to)3347-3357
Number of pages11
JournalJournal of Neuroscience
Volume30
Issue number9
DOIs
StatePublished - Mar 3 2010
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)

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    Ng, L., Lyubarsky, A., Nikonov, S. S., Ma, M., Srinivas, M., Kefas, B., St. Germain, D. L., Hernandez, A., Pugh Jr, E. N., & Forrest, D. (2010). Type 3 deiodinase, a thyroid-hormone-inactivating enzyme, controls survival and maturation of cone photoreceptors. Journal of Neuroscience, 30(9), 3347-3357. https://doi.org/10.1523/JNEUROSCI.5267-09.2010