Ontogeny of Thyroid Hormone Signaling in the Retina of Zebrafish: Effects of Thyroidal Status on Retinal Morphology, Cell Survival, and Color Preference

Int J Mol Sci. 2024 Nov 14;25(22):12215. doi: 10.3390/ijms252212215.

Abstract

The retina is crucial for converting light into neuronal signals for visual perception. Understanding the retina's structure, function, and development is essential for vision research. It is known that the thyroid hormone (TH) receptor type beta 2 (TRβ2) is a key element in the regulation of cone differentiation in the retina, but other elements of TH signaling, such as transporters and enzyme deiodinases, have also been implicated in retinal cell development and survival. In the present study, we investigated the expression profile of genes involved in TH signaling and analyzed the impact of thyroidal status on retinal morphology, opsin expression, cell death/proliferation profile, as well as color preference behavior during the early retina development of zebrafish larvae. mRNA expression analysis on dissected whole eyes revealed that TH signaling elements gradually increase during eye development, with dio3b being the component that shows the most dramatic change. Mutations generated by CRISPR/CAS9 in the dio3b gene, but not in the thrb gene, modifies the structure of the retina. Disruption in TH level reduces the cell number of the ganglion cell layer, increases cell death, and modifies color preference, emphasizing the critical importance of precise TH regulation by its signaling elements for optimal retinal development and function.

Keywords: deiodinases; retina development; thyroid hormone receptor; thyroid hormones; zebrafish.

MeSH terms

  • Animals
  • Cell Survival*
  • Gene Expression Regulation, Developmental
  • Iodide Peroxidase
  • Larva / genetics
  • Larva / metabolism
  • Retina* / metabolism
  • Signal Transduction*
  • Thyroid Hormones* / genetics
  • Thyroid Hormones* / metabolism
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / metabolism
  • Zebrafish* / genetics
  • Zebrafish* / metabolism

Substances

  • Thyroid Hormones
  • Zebrafish Proteins
  • iodothyronine deiodinase type III
  • Iodide Peroxidase

Grants and funding

This study was supported by UNAM PAPIIT IN206724 and IN210823; CONAHCyT Ciencia de Frontera, Paradigmas y Controversias de las Ciencias 2022 319880.