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Age-Dependent Changes of Monocarboxylate Transporter 8 Availability in the Postnatal Murine Retina

The thyroid hormones (TH) triiodothyronine (T3) and its prohormone thyroxine (T4) are crucial for retinal development and function, and increasing evidence points at TH dysregulation as a cause for retinal degenerative diseases. Thus, precise regulation of retinal TH supply is required for proper re...

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Autores principales: Henning, Yoshiyuki, Szafranski, Karol
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4999454/
https://www.ncbi.nlm.nih.gov/pubmed/27616981
http://dx.doi.org/10.3389/fncel.2016.00205
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author Henning, Yoshiyuki
Szafranski, Karol
author_facet Henning, Yoshiyuki
Szafranski, Karol
author_sort Henning, Yoshiyuki
collection PubMed
description The thyroid hormones (TH) triiodothyronine (T3) and its prohormone thyroxine (T4) are crucial for retinal development and function, and increasing evidence points at TH dysregulation as a cause for retinal degenerative diseases. Thus, precise regulation of retinal TH supply is required for proper retinal function, but knowledge on these mechanisms is still fragmentary. Several transmembrane transporters have been described as key regulators of TH availability in target tissues of which the monocarboxylate transporter 8 (MCT8), a high affinity transporter for T4 and T3, plays an essential role in the central nervous system. Moreover, in the embryonic chicken retina, MCT8 is highly expressed, but the postnatal availability of MCT8 in the mammalian retina was not reported to date. In the present study, spatiotemporal retinal MCT8 availability was examined in mice of different age. For this purpose, we quantified expression levels of Mct8 via Real-Time Reverse-Transcriptase PCR in mouse eyecups (C57BL/6) of juvenile and adult age groups. Additionally, age-dependent MCT8 protein levels were quantified via Western blotting and localized via immunofluorescence confocal microscopy. While no difference in Mct8 expression levels could be detected between age groups, MCT8 protein levels in juvenile animals were about two times higher than in adult animals based on Western blot analyses. Immunohistochemical analyses showed that MCT8 immunoreactivity in the eyecup was restricted to the retina and the retinal pigment epithelium. In juvenile mice, MCT8 was broadly observed along the apical membrane of the retinal pigment epithelium, tightly surrounding photoreceptor outer segments. Distinct immunopositive staining was also detected in the inner nuclear layer and the ganglion cell layer. However, in adult specimens, immunoreactivity visibly declined in all layers, which was in line with Western blot analyses. Since MCT8 was abundantly present in juvenile and about twofold lower in adult retinae, our findings suggest a pivotal role of MCT8 especially during postnatal maturation. The present study provides novel insights into age-dependent retinal TH supply, which might help to understand different aspects regarding retinal development, function, and disorders.
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spelling pubmed-49994542016-09-09 Age-Dependent Changes of Monocarboxylate Transporter 8 Availability in the Postnatal Murine Retina Henning, Yoshiyuki Szafranski, Karol Front Cell Neurosci Neuroscience The thyroid hormones (TH) triiodothyronine (T3) and its prohormone thyroxine (T4) are crucial for retinal development and function, and increasing evidence points at TH dysregulation as a cause for retinal degenerative diseases. Thus, precise regulation of retinal TH supply is required for proper retinal function, but knowledge on these mechanisms is still fragmentary. Several transmembrane transporters have been described as key regulators of TH availability in target tissues of which the monocarboxylate transporter 8 (MCT8), a high affinity transporter for T4 and T3, plays an essential role in the central nervous system. Moreover, in the embryonic chicken retina, MCT8 is highly expressed, but the postnatal availability of MCT8 in the mammalian retina was not reported to date. In the present study, spatiotemporal retinal MCT8 availability was examined in mice of different age. For this purpose, we quantified expression levels of Mct8 via Real-Time Reverse-Transcriptase PCR in mouse eyecups (C57BL/6) of juvenile and adult age groups. Additionally, age-dependent MCT8 protein levels were quantified via Western blotting and localized via immunofluorescence confocal microscopy. While no difference in Mct8 expression levels could be detected between age groups, MCT8 protein levels in juvenile animals were about two times higher than in adult animals based on Western blot analyses. Immunohistochemical analyses showed that MCT8 immunoreactivity in the eyecup was restricted to the retina and the retinal pigment epithelium. In juvenile mice, MCT8 was broadly observed along the apical membrane of the retinal pigment epithelium, tightly surrounding photoreceptor outer segments. Distinct immunopositive staining was also detected in the inner nuclear layer and the ganglion cell layer. However, in adult specimens, immunoreactivity visibly declined in all layers, which was in line with Western blot analyses. Since MCT8 was abundantly present in juvenile and about twofold lower in adult retinae, our findings suggest a pivotal role of MCT8 especially during postnatal maturation. The present study provides novel insights into age-dependent retinal TH supply, which might help to understand different aspects regarding retinal development, function, and disorders. Frontiers Media S.A. 2016-08-26 /pmc/articles/PMC4999454/ /pubmed/27616981 http://dx.doi.org/10.3389/fncel.2016.00205 Text en Copyright © 2016 Henning and Szafranski. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Henning, Yoshiyuki
Szafranski, Karol
Age-Dependent Changes of Monocarboxylate Transporter 8 Availability in the Postnatal Murine Retina
title Age-Dependent Changes of Monocarboxylate Transporter 8 Availability in the Postnatal Murine Retina
title_full Age-Dependent Changes of Monocarboxylate Transporter 8 Availability in the Postnatal Murine Retina
title_fullStr Age-Dependent Changes of Monocarboxylate Transporter 8 Availability in the Postnatal Murine Retina
title_full_unstemmed Age-Dependent Changes of Monocarboxylate Transporter 8 Availability in the Postnatal Murine Retina
title_short Age-Dependent Changes of Monocarboxylate Transporter 8 Availability in the Postnatal Murine Retina
title_sort age-dependent changes of monocarboxylate transporter 8 availability in the postnatal murine retina
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4999454/
https://www.ncbi.nlm.nih.gov/pubmed/27616981
http://dx.doi.org/10.3389/fncel.2016.00205
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