Thyroid hormone action is required for normal cone opsin expression during mouse retinal development

Cristiano N. Pessôa, Leticia A. Santiago, Diana A. Santiago, Danielle S. Machado, Fernando A.F. Rocha, Dora F. Ventura, Jan Nora Hokoç, Carmen C. Pazos-Moura, Fredric E. Wondisford, Patricia F. Gardino, Tania M. Ortiga-Carvalho

Research output: Contribution to journalArticle

Abstract

Purpose. The expression of S- and M-opsins in the murine retina is altered in different transgenic mouse models with mutations in the thyroid hormone receptor (TR)-|3 gene, demonstrating an important role of thyroid hormone (TH) in retinal development. Methods. The spatial expression of S- and M-opsin was compared in congenital hypothyroidism and in two different TR mutant mouse models. One mouse model contains a ligand- binding mutation that abolishes TH binding and results in constitutive binding to nuclear corepressors. The second model contains a mutation that blocks binding of coactivators to the AF-2 domain without affecting TH binding. Results. Hypothyroid newborn mice showed an increase in S-opsin expression that was completely independent of the genotype. Concerning M-opsin expression, hypothyroidism caused a significant decrease (P < 0.01) only in wild-type animals. When TR<β1 and -β were T3-binding defective, the pattern of opsin expression was similar to TR|3 ablation, showing increased S-opsin expression in the dorsal retina and no expression of M-opsin in the entire retina. In an unexpected finding, immunostaining for both opsins was detected when both subtypes of TRβ were mutated in the helix 12 AF-2 domain. Conclusions. The results show, for the first time, that the expression of S- and M-opsin is dependent on normal thyroid hormone levels during development.

Original languageEnglish (US)
Pages (from-to)2039-2045
Number of pages7
JournalInvestigative Ophthalmology and Visual Science
Volume49
Issue number5
DOIs
StatePublished - Apr 1 2008

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ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Pessôa, C. N., Santiago, L. A., Santiago, D. A., Machado, D. S., Rocha, F. A. F., Ventura, D. F., Hokoç, J. N., Pazos-Moura, C. C., Wondisford, F. E., Gardino, P. F., & Ortiga-Carvalho, T. M. (2008). Thyroid hormone action is required for normal cone opsin expression during mouse retinal development. Investigative Ophthalmology and Visual Science, 49(5), 2039-2045. https://doi.org/10.1167/iovs.07-0908