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A. Glaschke, M. Glösmann, L. Peichl; The Effect of Postnatal Hypothyroidism on Cone Opsin Expression in Mice. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1257.
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To study the effect of postnatal hypothyroidism on retinal development and the spatial patterning of cone opsin expression in the Pax8-/- mouse, a model for congenital hypothyroidism (Mansouri & Gruss, 1998). Thyroid hormone receptor beta 2 is expressed in cones; upon deletion of the receptor, all cones express the S opsin and no L opsin expression occurs (Ng et al., 2001). We were interested in the role of thyroid hormone (TH), the ligand of this receptor.
First, cone opsin expression was assessed up to postnatal week three in untreated Pax8-/-, Pax8+/-, and Pax8+/+ mice. Second, the effect of TH on cone opsin expression during development was assessed in hypothyroid Pax8-/- mice by daily subcutaneous injections of thyroxine (T4) for various time intervals from P1 up to postnatal week 12. Third, the effect of TH on the plasticity of cone opsin expression at adult ages was evaluated in Pax8-/- mice that were injected with T4, and in C57BL/6 mice that were treated with methimazole to induce hypothyroidism. The spatiotemporal expression of L and S opsins was assessed in isolated whole retinae using L and S opsin specific antisera, visualization was by double-immunofluorescence. L and S cone densities (1/mm²) were measured in several sampling fields in dorsal and ventral retina of each animal.
Development of the eye and retina during postnatal weeks 1-3 appeared normal in Pax8-/- mice. The only obvious retinal defect was a disturbed cone opsin expression pattern. All cones expressed the S opsin, and L opsin expression was reduced over the entire retina. T4 substitution in Pax8-/- mice (at developmental and adult ages) reversibly restored the wildtype pattern of cone opsin distribution until postnatal week 18. Termination of T4 substitution before week 8 reverted cone opsin expression to the hormone deficient (Pax8-/-) pattern. Methimazole treatment of adult C57/B6 J mice resulted in a cone pattern similar to that in Pax8-/- mice.
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