Without a doubt, one of the most fascinating and complex organs of the human body is the eye, second only to the brain. A very crucial component of eye function is the retina, the innermost, light-sensitive layer. It contains cells that trigger nerve activation from the optic nerve to the brain, where a visual image is finally formed. Such cells are called cone photoreceptors and are responsible for detecting light and translating it into colour. Our eye has three different subtypes of cone cells and they are defined by the type of visual pigment that they produce; blue, red and green. However, we are still unaware of the mechanism that drives the decision of these cells to become green, red or blue.
Despite developments in modern medicine, a large number of people are still affected by eye diseases as colour blindness, retinitis pigmentosa and macular degeneration. To address these unmet needs, Prof. Robert J. Johnston Jr.’s group at John Hopkins University has been studying these photoreceptor cells in the human eye. His group is primarily interested in unravelling the mechanisms of cell fate determination and investigate what drives cells transform into other, more specific types of cells. Despite cell fate biology being a rapidly growing field nowadays, these mechanisms are still largely unknown. We know that these specialized cells are very important in colour and daytime vision, but we still lack understanding about how these subtypes are initially generated. Interestingly, these cells seem to be the product of unique variation and random distribution across individuals, differing even between twins.
Current knowledge of the vertebrate eye has mostly been derived from the study of model organisms. However, the issue is that animals such as fish and mice have different structures within the eye, making model research difficult to apply to humans. The Johnston group tried to answer these questions by differentiating human stem cells into retinal cups. These cups contain all cell types of the human retina including the cone cells detecting green, blue and red light, thus allowing researchers to address specific questions regarding human eye development.
As seen in their latest publication in Science by lead author Kiara Eldred, once these retinal cups, or ‘organoids’, have formed over months, it was clear that photoreceptor cells first choose a fate of blue-detecting cells and then red/green detecting cells. Most importantly, however, the team found that the key regulator for this decision process is thyroid hormone signalling. Since the thyroid gland is absent from the dish, it seems that the whole process is regulated entirely by the eye itself. This can be validated in the clinic as preterm human babies with low levels of thyroid hormone have increased chances of colour vision defects.
With these results, potential therapies to treat human eye diseases, such as colour blindness, seem to be closer than ever. We will keep a close ‘eye’ on Prof. Johnston Jr.’s group for future publications and more exciting findings in the field.
This article was written by Manolis Solomonidis and edited by Karolina Zieba.
