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Developmental changes of cone opsin expression but not retinal morphology in the hypothyroid Pax8 knockout mouse
Anika Glaschke1, Martin Glösmann, Leo Peichl
1Max Planck Institute for Brain Research, Frankfurt am Main, Germany.
Purpose:
The effects of postnatal hypothyroidism on retinal development and spatial patterning of cone opsin expression were studied in Pax8-deficient mice. Pax8(-/-) mice are incapable of synthesizing thyroxine and serve as a model for congenital hypothyroidism.
Methods:
Pax8(-/-), Pax8(+/-), and Pax8(+/+) littermates were studied. Serum thyroid hormone levels, body weight, and eye size were measured. Retinal cell-type-specific antibodies were used on frozen sections to examine the postnatal development of the major retinal cell classes and of retinal structure. The expression of short-wavelength-sensitive (S) and middle-to-long-wavelength-sensitive (M) cone opsins was assessed with opsin antibodies on retinal sections and whole retinas. The pattern of S opsin mRNA was assessed by in situ hybridization.
Results:
In Pax8(-/-) mice, S opsin was upregulated in all cones, whereas M opsin was downregulated throughout the retina, the wild-type dorsoventral gradients of S and M opsin expression were absent. Otherwise, Pax8(-/-) mice showed no overt mutant phenotype in eye size, gross retinal anatomy, and the time-course of structural differentiation of retinal photoreceptors, horizontal cells, bipolars, amacrines, ganglion cells, and Müller glia cells.
Conclusions:
Pax8(-/-) mice show a pattern of cone opsin expression that differs substantially from the wild-type pattern, but exhibit no apparent alterations in general retinal development. The finding that a postnatal decrease in serum thyroid hormone yields changes in postnatal cone opsin expression is consistent with a ligand-dependent role of thyroid hormone receptor beta2 in S opsin repression and M opsin activation.
Insights
Congenital hypothyroidism in Pax8(-/-) mice alters cone opsin expression patterns in the retina. Despite changes in short-wavelength-sensitive and middle-to-long-wavelength-sensitive opsins, overall retinal development remains unaffected.
Area of Science:
- Ophthalmology
- Developmental Biology
- Endocrinology
Background:
- Congenital hypothyroidism, a condition affecting thyroid hormone synthesis, can impact development.
- Thyroid hormones play a crucial role in various developmental processes, including neural development.
- Retinal development and visual pigment expression are complex processes influenced by hormonal factors.
Purpose of the Study:
- To investigate the effects of postnatal hypothyroidism on retinal development.
- To examine the spatial patterning of cone opsin expression in the retina of hypothyroid mice.
- To utilize Pax8-deficient mice as a model for congenital hypothyroidism.
Main Methods:
- Studied Pax8(-/-), Pax8(+/-), and Pax8(+/+) littermates.
- Measured serum thyroid hormone levels, body weight, and eye size.
- Utilized cell-type-specific antibodies and in situ hybridization to analyze retinal structure and cone opsin expression (S opsin and M opsin).
Main Results:
- Pax8(-/-) mice exhibited altered expression of S opsin (upregulated) and M opsin (downregulated) in the retina.
- The normal dorsoventral gradients of S and M opsin expression were absent in Pax8(-/-) mice.
- No significant defects in overall eye size, retinal anatomy, or the differentiation of major retinal cell types were observed.
Conclusions:
- Postnatal hypothyroidism in Pax8(-/-) mice leads to substantial changes in cone opsin expression patterns.
- General retinal development and structural differentiation appear unaffected by congenital hypothyroidism in this model.
- Findings support a role for thyroid hormone receptor beta2 in regulating S and M opsin expression during retinal development.
