Scientists published a study in 2021 in which they reported that small brains created from stem cells in a laboratory developed rudimentary eye structures on their own. These tiny brain organoids, which were derived from human cells and grown in dishes, showed the growth of two optic cups that were symmetrical on both sides, similar to the way eye structures develop in human embryos. This finding may provide insights into the process of eye differentiation and development, as well as the causes of eye diseases.
In a statement made in 2021, neuroscientist Jay Gopalakrishnan from University Hospital Düsseldorf in Germany said that the study demonstrated the remarkable ability of brain organoids to form primitive sensory structures that are sensitive to light and contain cells similar to those found in the human body. These organoids could be used to study the interaction between the brain and eyes during embryo development, model congenital eye disorders, and generate retinal cells specific to individual patients for personalized drug testing and transplantation therapies.
Grown Mini Brains
Science Alert reported that the brain organoids are not actual brains in the way that you might think of them. They are small, three-dimensional structures created from induced pluripotent stem cells, which are cells taken from adult humans and reprogrammed into stem cells that have the potential to develop into many different types of tissue. In this case, the stem cells were induced to grow into clusters of brain tissue, but they do not have any thoughts, emotions, or consciousness. These "mini-brains" are used for research purposes where it would be impossible or unethical to use real brains, such as testing drug responses or studying cell development under certain adverse conditions.
In this study, Gopalakrishnan and his team were interested in studying eye development. Other scientists had previously used embryonic stem cells to grow optic cups, which are structures that develop into the majority of the eye during embryonic development, and had also created optic cup-like structures from induced pluripotent stem cells. Rather than directly growing these structures, Gopalakrishnan's team wanted to see if they could be grown as part of brain organoids, which would allow them to observe how the optic cups and brain tissue grow together rather than just growing optic cups in isolation.
Eye development is a complex process, and understanding it could provide insights into the molecular basis of early eye diseases, the researchers wrote in their paper. It is therefore important to study optic vesicles, which are the precursor to the eye and are attached to the forebrain and play a crucial role in proper eye formation. Previous research on organoids had shown the presence of retinal cells, but these did not develop optic structures. The team altered their protocols and did not try to force the development of purely neural cells at the early stages of neural differentiation. They also added retinol acetate to the culture medium to aid in eye development.
Brain organoids with optic cups at day 60 of development. (Gabriel et al., Cell Stem Cell, 2021)
Understanding the Brain
The team observed the formation of optic cups in the brain organoids as early as 30 days into development, and the structures were visible at 50 days. This timing is consistent with the development of eyes in human embryos, suggesting that these organoids could be useful for studying the details of this process. The optic cups contained various types of retinal cells that organized into neural networks that responded to light and even contained lens and corneal tissue. Additionally, the structures showed retinal connectivity to regions of the brain tissue.
Gopalakrishnan said that in the mammal brain, nerve fibers from retinal ganglion cells reach out to connect with their brain targets, which has never before been shown in an in vitro system. The team was able to reproduce this finding, as 73% of the 314 brain organoids they grew developed optic cups. The team hopes to develop ways to keep these structures viable for longer periods to conduct more in-depth research with the potential for significant impact.
The scientists wrote in their paper that optic vesicle-containing brain organoids that contain highly specialized neuronal cell types could be developed, potentially leading to the creation of personalized organoids and retinal pigment epithelial sheets for transplantation. They believe that these brain organoids, which can model retinopathies that result from early neurodevelopmental disorders, are the next generation of organoids. The study's analysis has been reported in the journal Cell Stem Cell.
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