Thyroid hormone signaling specifies cone subtypes in human retinalganoids this findings was published in the Journal Science, lay the foundation for the development of drugs for eye diseases such as color blindness and macular degeneration.
The cone-shaped light sensor in the eye is the "secret" for seeing colors, and its expression of optoprotein pigments can respond to different wavelengths of light. In the latest study, Robert Johnston, a developmental biologist at Johns Hopkins University, and his team focused on the three conical photoreceptors that allow people to see blue, red and green cones. These three subtypes are defined by the visual pigments they express: blue-vision protein (short wavelength; S), green-vision protein (medium wavelength; M) or red-vision protein (long wavelength; L). Mutations that affect the expression or function of the retina result in various forms of color blindness and retinal degeneration.
In the past, most visual studies have been done in mice and fish, but neither animal has daytime vision or color vision in humans. So Johnstons team used stem cells to create the "human eyes" they need. The organs and retina have similar distribution, expression pattern and conic subtype.
Tricolor vision distinguishes us from most other mammals said Kiara Eldred, the first author and a graduate student at Johns Hopkins University. "Our research is trying to figure out what special color vision these cells can give us.
Temporally regulated TH signaling specifies cone subtypes.
Over the past few months, as cells grew in the laboratory and matured into the retina, the team found blue cones first, then red and green cones. In these two cases, they found that the key of molecular switch was thyroid hormone level. Importantly, this hormone level is not controlled by the thyroid gland (because there is no thyroid gland in the dish), but by the eye itself.
This finding suggests that the differentiation of cone-shaped cells to their regulatory subtypes is regulated by thyroid hormones. This also explains why preterm infants have lower thyroid hormone levels and higher incidence of visual impairment due to lack of maternal supply.
Johnstons lab has been exploring the mechanisms that determine the fate of cells - what happens in the uterus, turning developing cells into specific types of cells. This is largely unknown to human biology. If we can answer the question about the fate of cell terminals, we can restore color vision to people who have damaged their photoreceptors Eldred said.
These findings are only the first step. In the future, the team hopes to use organ-like devices to further understand the mechanisms of color vision and other areas of the retina, such as macula. Because macular degeneration is one of the main causes of blindness, understanding the mechanism of macular formation is helpful to clinical treatment.
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