April 12, 2024

Lab-grown retinas provide insights into human color vision

Researchers have successfully grown human retinas in vitro and discovered the mechanisms behind the human-specific ability to see millions of colors. This finding sheds light on color blindness, age-related vision loss, and other diseases related to photoreceptor cells. The study also reveals how specific genes instruct the human retina to develop color-sensing cells, a process previously believed to be controlled by thyroid hormones.

The study, published in PLOS Biology, was conducted by a team led by Robert Johnston, an associate professor of biology. This breakthrough research offers a deeper understanding of what differentiates humans from other mammals in terms of visual perception.

Using retinal organoids grown from human stem cells, the researchers manipulated the cellular properties of the organoids to identify the role of a molecule called retinoic acid in determining whether a cone cell will specialize in sensing red or green light. This molecule was found to play a crucial role in the development of red cones, a type of cone that is unique to humans and closely related primates.

Previous theories suggested that red cones formed through a random process, where cells commit to sensing either green or red wavelengths. However, this study suggests that retinoic acid orchestrates a specific sequence of events within the eye that leads to the formation of red cones.

The team found that high levels of retinoic acid during early development of the organoids resulted in a higher ratio of green cones. Conversely, low levels of retinoic acid altered the genetic instructions of the retina and generated red cones later in development.

Although the study indicates that there may still be some randomness involved, the key finding is that the timing of retinoic acid production during development is crucial in understanding the formation of cone cells.

The research team also discovered that green and red cone cells are structurally similar, with the only distinguishing factor being a protein called opsin. Opsin detects light and communicates the perceived colors to the brain. Different types of opsins determine whether a cone cell becomes a green or red sensor. Despite the genetic differences between the two sensors, both green and red cone cells shared 96% identical genes.

Using a breakthrough technique, the researchers tracked changes in the ratio of green and red cone cells in the retinal organoids over a span of 200 days. This allowed them to identify subtle genetic differences that contribute to these variations.

Furthermore, the researchers mapped the varying ratios of green and red cone cells in the retinas of 700 adults. They discovered significant differences in these ratios among individuals, which was an unexpected finding.

While scientists still do not fully understand how these variations in cone cell ratios do not affect visual perception, the study provides valuable insights that may contribute to the understanding and treatment of conditions such as macular degeneration, which causes the loss of light-sensing cells in the central retina.

The researchers at Johns Hopkins University are collaborating with other labs within the institution to investigate how cone cells and other retinal cells connect to the nervous system. The ultimate goal of this research is to develop therapies for individuals affected by vision problems.

While there is still much work to be done, Johnston is optimistic about the potential applications of this research in helping individuals with vision impairments. The ability to generate different types of retinal cells through the manipulation of retinoic acid holds promise for future treatments in the field of ophthalmology.

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