Is This Petri Dish Looking At Me?

(Posted on Tuesday, October 19, 2021)

This story is part of an occasional series on the current progression in Regenerative Medicine. In 1999, I defined regenerative medicine as the collection of interventions that restore to normal function tissues and organs that have been damaged by disease, injured by trauma, or worn by time. I include a full spectrum of chemical, gene and protein-based medicines, cell-based therapies, and biomechanical interventions that achieve that goal.

One of the more significant advances in understanding human organs and cell biology is the ability to grow miniature versions of human organs in a cell culture. These are called organoids and are an emerging area of research that allows scientists to understand the root causes of diseases, how to treat them, and potentially how to rebuild the organs themselves.

Of all the organs of interest, however, the brain is possibly the most interesting and cryptic. A recent report published by scientists from the Institute of Human Genetics at Heinrich-Heine University displays significant progress in the development of not only brain organoids, but surprisingly, ones with rudimentary eyes.

Our sensory organs, particularly our eyes and our ears, are extensions of the brain. Though they are often thought of as discrete structures, the eye’s retinal cells are classified as neurons. Pure brain organoids have been grown in the past. However, because of the relationship between the eyes and the brain, researchers at Heinrich-Heine University were particularly interested in addressing the question of whether we can grow brain organoids that contain these rudimentary optic structures.

The researchers began by first forming generic brain organoids. As expected, the organoids did not form any visible optic vesicles. However, they did display genetic markers for retinal and other eye cells. This prompted the researchers to alter their approach.

Previous studies have demonstrated that a crucial signal for retinal cell development is retinoic acid. Retinoic acid inhibits brain tissue growth in the area where the optic cup develops. With this information, researchers first conditioned pluripotent stem cells to differentiate into neural cells to form the generic brain organoid. As the brain organoid was forming, they introduced retinoic acid into the cell culture.

To their surprise, after 60 days the brain organoid formed highly pigmented areas that resembled a pair of eyes. Analysis of the organoid revealed that with the addition of retinoic acid, eight different cell populations were produced. These included the generic brain organoid cell types along with cells responsible for the formation of the optic cup and cells necessary for retina development.

Not only this, but certain cells were responsive to light. In the human brain, particularly in the retina, there exist cells that will display higher or lower activity levels in the presence of light. These are called photosensitive cells. When photosensitive cells in the brain are suddenly exposed to bright lights, they are rendered inactive. After being exposed to darkness, photosensitive cells will reactivate and display normal responses to light. Researchers tested this ability in the organoids and found that they were able to recover their photosensitivity, matching the light responses of eyes in vivo.

This study is an exciting step forward not only for brain research, but also for research about the highly specialized organ of the eye. With this progress, the hope is that researchers will have the foundation to push further and begin to understand how eyes are generated. This may have a direct impact on our understanding of heritable diseases in the eyes and how to repair optic defects acquired during our lives.

Read the full article on Forbes