ESPEYB16 3. Thyroid Thyroid Hormone Action (3 abstracts)
3.2. Thyroid hormone signaling specifies cone subtypes in human retinal organoids
Eldred KC , Hadyniak SE , Hussey KA , Brenerman B , Zhang PW , Chamling X , Sluch VM , Welsbie DS , Hattar S , Taylor J , Wahlin K , Zack DJ & Johnston RJ Jr
To read the full abstract: Science. 2018;362(6411).
Here, developmental regulation of deiodinases DIO2 and DIO3 were identified as main regulators of thyroid hormone dependent sequential cone subtype specification in human retinal organoids. Either complete loss of thyroid hormone signaling or non-physiologically high thyroid hormone levels completely suppressed either medium and long wavelength cones or short wavelength cones, respectively.
Cone differentiation develops in a timely regulated manner. First, short wavelength cones develop in a low thyroid hormone context. By increasing thyroid hormone levels, short wavelength cone specification is blocked, while medium/long wavelength cone specification is induced. This article is a proof of concept of thyroid hormone dependent retinal cone differentiation in the human described earlier in the mouse model [1] and provides molecular evidence for retinal regulation of thyroid hormone concentrations by dynamic DIO2 and DIO3 gene expression during development of the human retina. It is further providing molecular evidence for direct effect of in utero hypothyroidism on visual abilities in the fetus that have been described in children exposed to maternal hypothyroidism in utero, children with congenital hypothyroidism, and preterm with hypothyroxinemia. Systematic studies revealed decreased contrast sensitivity and color vision processing [2, 3].
From this paper, we learn as clinicians to keep an eye on the vision of children exposed to hypo- or hyperthyroidism in utero.
References: 1. Roberts MR, Srinivas M, Forrest D, Morreale de Escobar G, Reh TA. Making the gradient: thyroid hormone regulates cone opsin expression in the developing mouse retina. Proc Natl Acad Sci U S A. 2006;103:6218–23. PMID: 16606843.
2. Mirabella G, Westall CA, Asztalos E, Perlman K, Koren G, Rovet J. Development of contrast sensitivity in infants with prenatal and neonatal thyroid hormone insufficiencies. Pediatr Res. 2005;57:902–7. PMID: 15774837.
3. Simic N, Westall C, Asztalos EV, Rovet J. Visual abilities at 6 months in preterm infants: impact of thyroid hormone deficiency and neonatal medical morbidity. Thyroid. 2010;20:309–15. PMID: 20144040.
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ESPE Yearbook of Paediatric Endocrinology
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