Light Helps Retinal Cells Mature, Yet Scientists Have So Far Overlooked It in Laboratory Models

Retinal organoids, sometimes referred to as “mini retinas,” have in recent years become an important tool for studying the development of the human eye and retinal diseases. They are also used to test new therapeutic approaches and, in the future, could serve as a source of cells for cell therapy. However, they have one major limitation. Even after many months of cultivation, their cells do not reach the same level of maturity as cells in the human retina.

“It seemed paradoxical to us that we are trying to create the most faithful possible model of the human retina in the laboratory, while cultivating it in darkness for practically its entire development,” says Tomáš Bárta from the Faculty of Medicine at Masaryk University. “So we asked ourselves a simple question: what happens if we give the developing retina exactly the stimulus it is naturally designed to respond to – light?” The scientists exposed the mini retinas to different lighting regimes and monitored how light affected their development.

The most pronounced effect was observed with regularly flashing light. Just one week of such stimulation promoted the maturation of photoreceptors – the light-sensitive cells of the retina. The cells developed more advanced structures for detecting light, while the activity of genes associated with their maturation and function also changed. Photoreceptors exposed to light also more closely resembled the properties of cells in the adult human retina than cells cultured in darkness. The improvement was also reflected in the functioning of the mini retina. The scientists measured the activity of nerve cells using thousands of microscopic electrodes and found that light stimulation improved their responses.

“What surprised us most was that light did not trigger merely a short-term cellular response. This suggests that light may be more than just a stimulus detected by photoreceptors during their development,” says Tomáš Bárta, who leads a research group at the Department of Histology and Embryology at the Faculty of Medicine of Masaryk University investigating how stem cells form retinal tissues.

An independent study by a team from Radboud University Medical Center in Nijmegen, the Netherlands, reached a similar conclusion to the study by the Brno-based scientists, which was published in the journal Nature Communications. While the Masaryk University researchers primarily investigated the effects of short-term stimulation using different light regimes, the Dutch team exposed mini retinas to light regularly for several months. Using different experimental approaches, the two studies therefore point to the same principle: for developing photoreceptors, light may not only be a stimulus they detect but may also influence their maturation.

The ability to produce more mature photoreceptors in the laboratory could improve the use of retinal organoids in studying inherited retinal diseases and testing new drugs. In the future, light stimulation could also help prepare cells grown from stem cells for cell therapies for degenerative retinal diseases. The insufficient maturity of these cells may be one of the obstacles to successful transplantation.

“When culturing cells, we often focus on the composition of the culture medium and on the molecules that regulate their development. But sometimes we may overlook an equally important part of their natural environment,” reflects Tomáš Bárta. “In the case of the retina, that stimulus is light.” Another advantage of light stimulation is its simplicity. It does not require genetic modification of the cells or the addition of other substances to the culture medium, and its intensity and pattern can be precisely controlled and adapted to different stages of mini-retina development.