Type 3 deiodinase, a thyroid-hormone-inactivating enzyme, controls survival and maturation of cone photoreceptors.
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.
Ng
Lily
L
National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Clinical Endocrinology Branch, Bethesda, Maryland 20892-1772, USA.
Lyubarsky
Arkady
A
Nikonov
Sergei S
SS
Ma
Michelle
M
Srinivas
Maya
M
Kefas
Benjamin
B
St Germain
Donald L
DL
Hernandez
Arturo
A
Pugh
Edward N
EN
Forrest
Douglas
D
D000818:Animals; D016923:Cell Death / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D007453:Iodide Peroxidase / Q000235:genetics*; D008027:Light; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D055355:Opsins / Q000378:metabolism; D010775:Photic Stimulation; D012160:Retina / Q000166:cytology / Q000201:enzymology* / Q000254:growth & development*; D017949:Retinal Cone Photoreceptor Cells / Q000166:cytology / Q000201:enzymology* / Q000528:radiation effects; D037042:Thyroid Hormone Receptors beta / Q000378:metabolism; D013963:Thyroid Hormones / Q000378:metabolism*; D014785:Vision, Ocular / Q000235:genetics
D055355:Opsins; D037042:Thyroid Hormone Receptors beta; D013963:Thyroid Hormones; C117274:iodothyronine deiodinase type III; D007453:Iodide Peroxidase