An international research team have used induced pluripotent stem cells (iPSCs) to grow brain organoids that develop key structures of the eye. This could lead to a better understanding of eye development, aid in the advancement of therapies, and shows that iPSCs have an intrinsic capability to self-organise into complex biological structures including the brain.
Senior author Professor Jay Gopalakrishnan, of the University Hospital Düsseldorf, Germany said 'These organoids can help to study brain-eye interactions during embryo development, model congenital retinal disorders, and generate patient-specific retinal cell types for personalised drug testing and transplantation therapies.'
The team were able to generate 314 brain organoids across 16 batches with 72 percent of them forming optic vesicles. These optic vesicle-containing organoids contained primitive cornea and lens-like cells (which are structures at the front of the eye), pigmented retina (the part of the eye that receives light), and neuron-like projections (similar to the optic nerve) which responded to light.
It was previously thought that complex, structured organoid formation required specific chemical direction. While the organoids first created using methods designed by other researchers, these scientists found adding retinal acetate to the culture medium more successful. They found that after 30 days these brain organoids developed symmetrical optic cup vesicles which progressed into visible structures at 50-60 days, in line with human embryo development.
This provides a breakthrough in studying embryonic development, with Professor Gopalakrishnan saying 'in the mammalian brain, nerve fibres of retinal ganglion cells reach out to connect with their brain targets, an aspect that has never before been shown in an in vitro system'.
Although immature retinas have previously been grown from stem cells, this study, published in Cell Stem Cell, is the first to grow integrated eye-like structures. These optic cups are only representative of the immature eye and researchers are now looking into ways to extend the viability of these organoids to allow the development of more mature eye structures. More work is also needed to be able to reliably reproduce these results using iPSCs from different donors.
These developments can help in the study of inherited eye disorders, provide a model for testing new drugs, and could help in the production of personalised transplantation therapies.