| Type 3 deiodinase, a thyroid-hormone-inactivating enzyme, controls survival and maturation of cone photoreceptors. | |
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MedLine Citation:
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PMID: 20203194 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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, approximately 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 beta2 (TRbeta2) as deletion of TRbeta2 rescues cones in Dio3(-/-) mice. However, rescued cones respond to short but not longer wavelength light because TRbeta2 under moderate hormonal stimulation normally induces M opsin and controls the patterning of M and 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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Authors:
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Lily Ng; Arkady Lyubarsky; Sergei S Nikonov; Michelle Ma; Maya Srinivas; Benjamin Kefas; Donald L St Germain; Arturo Hernandez; Edward N Pugh; Douglas Forrest |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural |
Journal Detail:
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Title: The Journal of neuroscience : the official journal of the Society for Neuroscience Volume: 30 ISSN: 1529-2401 ISO Abbreviation: J. Neurosci. Publication Date: 2010 Mar |
Date Detail:
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Created Date: 2010-03-05 Completed Date: 2010-05-05 Revised Date: 2010-09-07 |
Medline Journal Info:
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Nlm Unique ID: 8102140 Medline TA: J Neurosci Country: United States |
Other Details:
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Languages: eng Pagination: 3347-57 Citation Subset: IM |
Affiliation:
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National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Clinical Endocrinology Branch, Bethesda, Maryland 20892-1772, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Death / genetics Cell Differentiation / genetics Cell Survival / genetics Female Gene Expression Regulation, Developmental / genetics Iodide Peroxidase / genetics* Light Male Mice Mice, Knockout Opsins / metabolism Photic Stimulation Retina / cytology, enzymology*, growth & development* Retinal Cone Photoreceptor Cells / cytology, enzymology*, radiation effects Thyroid Hormone Receptors beta / metabolism Thyroid Hormones / metabolism* Vision, Ocular / genetics |
| Grant Support | |
ID/Acronym/Agency:
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DK42271/DK/NIDDK NIH HHS; HD09020/HD/NICHD NIH HHS; ZIA DK047036-03/DK/NIDDK NIH HHS; ZIA DK047037-03/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Opsins; 0/Thyroid Hormone Receptors beta; 0/Thyroid Hormones; EC 1.11.1.-/iodothyronine deiodinase type III; EC 1.11.1.8/Iodide Peroxidase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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