Human brain organoids created from induced pluripotent stem cells (IPSCs) have been engineered to develop optic vesicles that respond to light.
Development of the eyes in embryogenesis is a complex process. During development, optic vesicles form which are the primordium of the eye, and their proximal end is attached to the forebrain, and is essential for proper eye formation. Previous research has shown it is possible to generate human IPSCs and differentiate them to create the optic cup. The optic cup gives rise to the human retina, but until this study, optic cups have not been generated and functionally integrated into human brain organoids.
The researchers modified a technique they had previously used to generate neural tissue from human IPSCs. They found that optic cups spontaneously developed from the front of the brain-like region, which showed the intrinsic self-patterning ability of iPSCs in complex biological processes. Optic cups formed in as little as 30 days, and then matured into structures that were clearly visible at around 50 days, which is a similar time frame to what is seen in normal human embryonic development.
IPSCs were generated from cells harvested from 4 donors, and across 16 independent batches the researchers generated 314 human brain organoids. 72% of those human brain organoids generated optic cups that were light sensitive. The structures formed had a diverse range of retinal cell types, had electrically active neural networks, were light sensitive, showed retinal connectivity to brain tissue, and contained lens and corneal tissue. This is the first time that nerve fibers of retinal ganglion cells have reached out to connect with their brain targets in an in vitro study.
Optic vesicle-containing brain organoids could potentially give researchers a model of eye development that could be used to study the mechanisms responsible for disorders of the retina.
“Our work highlights the remarkable ability of brain organoids to generate primitive sensory structures that are light sensitive and harbor cell types similar to those found in the body,” said Jay Gopalakrishnan, PhD, group leader of the Laboratory for Centrosome and Cytoskeleton Biology at University Hospital Düsseldorf. “These organoids can help to study brain-eye interactions during embryo development, model congenital retinal disorders, and generate patient-specific retinal cell types for personalized drug testing and transplantation therapies.”
The researchers are currently working on strategies for keeping the optic vesicles viable or long periods to make them suitable for use in medical research.
You can read more about the research in the paper – Human brain organoids assemble functionally integrated bilateral optic vesicles – which was recently published in Cell Stem Cell. DOI: 10.1016/j.stem.2021.07.010