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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; Thyroid Hormone Action Is Required for Normal Cone Opsin Expression during Mouse Retinal Development. Invest. Ophthalmol. Vis. Sci. 2008;49(5):2039-2045. doi: 10.1167/iovs.07-0908.
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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)-β 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 TRβ1 and -β2 were T3-binding defective, the pattern of opsin expression was similar to TRβ 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.
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