Postnatal Thyroid Hormone Supplementation Rescues Developmental Abnormalities Induced by Congenital-Neonatal Hypothyroidism in the Rat Retina

Pinazo-Durán,; Iborra, Francisco J.; Pons, S; Sevilla-Romero, Enrique; Gallego-Pinazo, Roberto; Múñoz, Alberto

doi:10.1159/000086863

Cited by 26 publications

(20 citation statements)

References 69 publications

(58 reference statements)

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“…Studies in rats have shown that pharmacologically induced hypothyroidism during the gestation and suckling period results in reduced eye size, delayed retinal development and morphological abnormalities in photoreceptors as well as in the inner retina, including reduced cell densities in the INL and GCL [11–14]. The time window for these wide-ranging effects of hypothyroidism can be narrowed down to the prenatal period.…”

Section: Discussionmentioning

confidence: 99%

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Thyroid Hormone Signaling in the Mouse Retina

et al. 2016

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Thyroid hormone is a crucial regulator of gene expression in the developing and adult retina. Here we sought to map sites of thyroid hormone signaling at the cellular level using the transgenic FINDT3 reporter mouse model in which neurons express β-galactosidase (β-gal) under the control of a hybrid Gal4-TRα receptor when triiodothyronine (T3) and cofactors of thyroid receptor signaling are present. In the adult retina, nearly all neurons of the ganglion cell layer (GCL, ganglion cells and displaced amacrine cells) showed strong β-gal labeling. In the inner nuclear layer (INL), a minority of glycineric and GABAergic amacrine cells showed β-gal labeling, whereas the majority of amacrine cells were unlabeled. At the level of amacrine types, β-gal labeling was found in a large proportion of the glycinergic AII amacrines, but only in a small proportion of the cholinergic/GABAergic ‘starburst’ amacrines. At postnatal day 10, there also was a high density of strongly β-gal-labeled neurons in the GCL, but only few amacrine cells were labeled in the INL. There was no labeling of bipolar cells, horizontal cells and Müller glia cells at both stages. Most surprisingly, the photoreceptor somata in the outer nuclear layer also showed no β-gal label, although thyroid hormone is known to control cone opsin expression. This is the first record of thyroid hormone signaling in the inner retina of an adult mammal. We hypothesize that T3 levels in photoreceptors are below the detection threshold of the reporter system. The topographical distribution of β-gal-positive cells in the GCL follows the overall neuron distribution in that layer, with more T3-signaling cells in the ventral than the dorsal half-retina.

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Section: Discussionmentioning

confidence: 99%

“…Prenatally, TH is an important regulator in the normal development of the eye and retina [11–14]. Postnatally, TH is crucial for the differentiation of spectral cone types.…”

Section: Introductionmentioning

confidence: 99%

Thyroid Hormone Signaling in the Mouse Retina

et al. 2016

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“…, 2007). Chemically induced congenital and neonatal hypothyroidism significantly reduces thickness, layering, volume, cell number and nuclear volumes in the retinas of Wistar rats (Pinazo‐Duran et al. , 2005).…”

Section: Discussionmentioning

confidence: 99%

Lack of protein‐tyrosine sulfation disrupts photoreceptor outer segment morphogenesis, retinal function and retinal anatomy

Sherry

Murray

Kanan

et al. 2010

Eur J of Neuroscience

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To investigate the role(s) of protein-tyrosine sulfation in the retina, we examined retinal function and structure in mice lacking tyrosylprotein sulfotransferases (TPST) 1 and 2. Tpst double knockout (DKO; Tpst1 −/− /Tpst2 −/− ) retinas had drastically reduced electroretinographic responses, although their photoreceptors exhibited normal responses in single cell recordings. These retinas appeared normal histologically; however, the rod photoreceptors had ultrastructurally abnormal outer segments, with membrane evulsions into the extracellular space, irregular disc membrane spacing, and expanded intradiscal space. Photoreceptor synaptic terminals were disorganized in Tpst DKO retinas, but established ultrastructurally normal synapses, as did bipolar and amacrine cells; however, the morphology and organization of neuronal processes in the inner retina were abnormal. These results indicate that protein-tyrosine sulfation is essential for proper outer segment morphogenesis and synaptic function, but is not critical for overall retinal structure or synapse formation, and may serve broader functions in neuronal development and maintenance.

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“…It regulates intrinsic mechanisms for controlling retinal cytoarchitecture and layering [10]. As Gamborino et al [11] demonstrated in a rat model, the photoreceptor and ganglion cell layer thickness displayed significantly lower values in congenital-neonatal hypothyroidism.…”

Section: Discussionmentioning

confidence: 99%

Ocular changes in primary hypothyroidism

et al. 2009

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BackgroundTo determine the ocular changes related to hypothyrodism in newly diagnosed patients without orbitopathy.FindingsThirty-three patients diagnosed to have primary overt hypothyroidism were enrolled in the study. All subjects were assigned to underwent central corneal thickness (CCT), anterior chamber volume, depth and angle measurements with the Scheimpflug camera (Pentacam, Oculus) and cup to disc ratio (C/D), mean retinal thickness and mean retinal nerve fiber layer (RNFL) thickness measurements with optical coherence tomography (OCT) in addition to ophthalmological examination preceeding the replacement therapy and at the 1st, 3rd and 6th months of treatment.The mean age of the patients included in the study were 40.58 ± 1.32 years. The thyroid hormone levels return to normal levels in all patients during the follow-up period, however the mean intraocular pressure (IOP) revealed no significant change. The mean CCT was 538.05 ± 3.85 μ initially and demonstrated no statistically significant change as the anterior chamber volume, depth and angle measurements did. The mean C/D ratio was 0.29 ± 0.03 and the mean retinal thickness was 255.83 ± 19.49 μ initially and the treatment did not give rise to any significant change. The mean RNFL thickness was also stable during the control visits, so no statistically significant change was encountered.ConclusionsNeither hypothyroidism, nor its replacement therapy gave rise to any change of IOP, CCT, anterior chamber parameters, RNFL, retinal thickness and C/D ratio.

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Postnatal Thyroid Hormone Supplementation Rescues Developmental Abnormalities Induced by Congenital-Neonatal Hypothyroidism in the Rat Retina

Cited by 26 publications

References 69 publications

Thyroid Hormone Signaling in the Mouse Retina

Thyroid Hormone Signaling in the Mouse Retina

Lack of protein‐tyrosine sulfation disrupts photoreceptor outer segment morphogenesis, retinal function and retinal anatomy

Ocular changes in primary hypothyroidism

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