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 language | English (US) |
|---|---|
| Pages (from-to) | 3347-3357 |
| Number of pages | 11 |
| Journal | Journal of Neuroscience |
| Volume | 30 |
| Issue number | 9 |
| DOIs | |
| State | Published - Mar 3 2010 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Neuroscience(all)
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Type 3 deiodinase, a thyroid-hormone-inactivating enzyme, controls survival and maturation of cone photoreceptors. / Ng, Lily; Lyubarsky, Arkady; Nikonov, Sergei S.; Ma, Michelle; Srinivas, Maya; Kefas, Benjamin; St. Germain, Donald L.; Hernandez, Arturo; Pugh Jr, Edward N; Forrest, Douglas.
In: Journal of Neuroscience, Vol. 30, No. 9, 03.03.2010, p. 3347-3357.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Type 3 deiodinase, a thyroid-hormone-inactivating enzyme, controls survival and maturation of cone photoreceptors
AU - Ng, Lily
AU - Lyubarsky, Arkady
AU - Nikonov, Sergei S.
AU - Ma, Michelle
AU - Srinivas, Maya
AU - Kefas, Benjamin
AU - St. Germain, Donald L.
AU - Hernandez, Arturo
AU - Pugh Jr, Edward N
AU - Forrest, Douglas
PY - 2010/3/3
Y1 - 2010/3/3
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=77749343305&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.5267-09.2010
DO - 10.1523/JNEUROSCI.5267-09.2010
M3 - Article
C2 - 20203194
AN - SCOPUS:77749343305
VL - 30
SP - 3347
EP - 3357
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 9
ER -