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[PMID]: | 28428265 |
[Au] Autor: | Ma H; Yang F; Butler MR; Belcher J; Redmond TM; Placzek AT; Scanlan TS; Ding XQ |
[Ad] Endereço: | Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA. |
[Ti] Título: | Inhibition of thyroid hormone receptor locally in the retina is a therapeutic strategy for retinal degeneration. |
[So] Source: | FASEB J;31(8):3425-3438, 2017 Aug. | [Is] ISSN: | 1530-6860 |
[Cp] País de publicação: | United States |
[La] Idioma: | eng |
[Ab] Resumo: | Thyroid hormone (TH) signaling regulates cell proliferation, differentiation, and metabolism. Recent studies have implicated TH signaling in cone photoreceptor viability. Using mouse models of retinal degeneration, we demonstrated that antithyroid drug treatment and targeting iodothyronine deiodinases (DIOs) to suppress cellular tri-iodothyronine (T3) production or increase T3 degradation preserves cones. In this work, we investigated the effectiveness of inhibition of the TH receptor (TR). Two genes, and , encode TRs; 2 has been associated with cone viability. Using TR antagonists and deletion, we examined the effects of TR inhibition. Systemic and ocular treatment with the TR antagonists NH-3 and 1-850 increased cone density by 30-40% in the mouse model of Leber congenital amaurosis and reduced the number of TUNEL cells. Cone survival was significantly improved in and (a model of achromatopsia with defect) mice with deletion. Ventral cone density in and / mice was increased by 1- to 4-fold, compared with age-matched controls. Moreover, the expression levels of TR were significantly higher in the cone-degeneration retinas, suggesting locally elevated TR signaling. This work shows that the effects of antithyroid treatment or targeting DIOs were likely mediated by TRs and that suppressing TR protects cones. Our findings support the view that inhibition of TR locally in the retina is a therapeutic strategy for retinal degeneration management.-Ma, H., Yang, F., Butler, M. R., Belcher, J., Redmond, T. M., Placzek, A. T., Scanlan, T. S., Ding, X.-Q. Inhibition of thyroid hormone receptor locally in the retina is a therapeutic strategy for retinal degeneration. |
[Mh] Termos MeSH primário: |
Antitireóideos/farmacologia Metimazol/farmacologia Receptores dos Hormônios Tireóideos/antagonistas & inibidores Retina/metabolismo Degeneração Retiniana/tratamento farmacológico
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[Mh] Termos MeSH secundário: |
Animais Antitireóideos/uso terapêutico Fatores de Transcrição de Zíper de Leucina Básica/genética Fatores de Transcrição de Zíper de Leucina Básica/metabolismo Morte Celular Modelos Animais de Doenças Proteínas do Olho/genética Proteínas do Olho/metabolismo Deleção de Genes Regulação da Expressão Gênica/efeitos dos fármacos Regulação da Expressão Gênica/fisiologia Metimazol/uso terapêutico Camundongos Camundongos Endogâmicos C57BL Camundongos Knockout Fenoxiacetatos/farmacologia Receptores dos Hormônios Tireóideos/genética Receptores dos Hormônios Tireóideos/metabolismo Células Fotorreceptoras Retinianas Cones/metabolismo Degeneração Retiniana/metabolismo Degeneração Retiniana/patologia Retinoblastoma Tri-Iodotironina cis-trans-Isomerases/genética cis-trans-Isomerases/metabolismo
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[Pt] Tipo de publicação: | JOURNAL ARTICLE |
[Nm] Nome de substância:
| 0 ((4-(4-hydroxy-3-isopropyl-5-(4-nitrophenylethynyl)benzyl)-3,5-dimethylphenoxy)acetic acid); 0 (Antithyroid Agents); 0 (Basic-Leucine Zipper Transcription Factors); 0 (Eye Proteins); 0 (Nrl protein, mouse); 0 (Phenoxyacetates); 0 (Receptors, Thyroid Hormone); 06LU7C9H1V (Triiodothyronine); 554Z48XN5E (Methimazole); EC 3.1.1.64 (retinoid isomerohydrolase); EC 5.2.- (cis-trans-Isomerases) |
[Em] Mês de entrada: | 1710 |
[Cu] Atualização por classe: | 171111 |
[Lr] Data última revisão:
| 171111 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 170422 |
[St] Status: | MEDLINE |
[do] DOI: | 10.1096/fj.201601166RR |
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