Two independent studies show that controlled light exposure promotes the maturation of photoreceptor cells in retinal organoids. The findings could help researchers develop better human models for studying retinal diseases and testing new treatments.
Human mini-retinas grown in the laboratory usually develop in the dark. Yet the retina’s natural function is to detect light. Researchers from Radboudumc and international collaborators therefore asked a simple question: could exposing these mini-retinas to light help them mature?
Two independent studies, published in Communications Biology and Nature Communications, now show that it can. Despite using different types of light stimulation, both research teams found that light promoted the maturation of photoreceptors, the cells in the retina that detect light.
The results could help address an important challenge in retinal research. Human retinal organoids can take many months to develop sufficiently mature photoreceptors for studying disease and evaluating potential treatments.
"It seems almost obvious in hindsight that light might matter for an organ whose main function is to respond to light, but retinal organoids are normally cultured in darkness," says Alex Garanto, research group leader at the Department of Pediatrics of Radboudumc. "Seeing the same principle emerge from two independent studies gives us much stronger reason to explore light as part of how we grow these models."
Creating better models of the human retina
Retinal organoids are small, three-dimensional models of the human retina grown from induced pluripotent stem cells. These stem cells can develop into different cell types, allowing researchers to recreate important aspects of human retinal development in the laboratory.
Over the past decade, retinal organoids have become valuable tools for studying how the retina develops, investigating inherited retinal diseases, and testing potential treatments. They may also contribute to the development of cell-based therapies.
Their slow development and maturation remains an important limitation. It typically takes around 240 days or longer for retinal organoids to develop relatively mature photoreceptors. This makes experiments lengthy and costly and can slow down research into new treatments.
Two research teams led by Alex Garanto at Radboudumc and Tomáš Bárta at Masaryk University in Czechia independently investigated whether light itself could help photoreceptors mature.
Different types of light, similar results
In the Radboudumc study, PhD candidate Edwin van Oosten and colleagues exposed retinal organoids to six hours of white light each day over several months. Long-term light exposure increased the expression of genes and proteins associated with mature photoreceptors and promoted the development of rod photoreceptor cells, which are particularly important for vision in low-light conditions. The researchers found no signs that the treatment caused cellular stress or damage.
In a separate study, Canan Celiker and colleagues investigated whether a more structured light signal could influence retinal development. The researchers exposed retinal organoids to rhythmic flickering light and found that stimulation at a specific frequency enhanced photoreceptor maturation at several levels.
The stimulated organoids developed more advanced light-sensing structures, showed more mature patterns of gene activity, and demonstrated improved signaling to other retinal neurons.
"What is striking is that the two teams used quite different forms of light stimulation, yet both saw improved photoreceptor maturation," says Edwin van Oosten, PhD researcher at Radboudumc and first author of the Communications Biology study. "That suggests that light is not only something mature photoreceptors respond to. It may actually help guide their development."
Better models for retinal disease
The fact that two independent research teams reached similar conclusions strengthens the evidence that light exposure can influence retinal development in the laboratory.
More mature retinal organoids more closely resemble the human retina and could therefore provide better models for investigating retinal diseases. This is particularly relevant for inherited retinal disorders, many of which affect photoreceptors and can lead to progressive vision loss.
Improving maturation could also make it easier to study disease mechanisms and evaluate potential treatments, including gene therapies and cell replacement strategies.
"Maturation is one of the main bottlenecks when working with retinal organoids," Garanto explains. "If we can improve that process with something as relatively simple as controlled light exposure, we can create better disease models and potentially shorten the time needed to study new treatments."
The researchers will now further investigate how light stimulation can best be incorporated into retinal organoid culture protocols to better understand disease. Ultimately, controlled light exposure could offer a relatively simple and scalable way to generate more mature human retinal models.
Support for the research
The Radboudumc study was conducted as part of the RoC-ME consortium within the Human Measurement Models 2.0 program. This strategic program is supported by the Association of Collaborating Health Foundations (SGF), NWO Domain Applied and Engineering Sciences, and the Netherlands Organisation for Health Research and Development (ZonMw).
The collaborative project is also co-funded through the PPP Allowance made available by Health~Holland, Top Sector Life Sciences & Health, to SGF to stimulate public-private partnerships. Additional support was provided by Oogfonds and Proefdiervrij.
About the publications
van Oosten EM, Kieboom W, Hoogendoorn ADM, Berendsen SL, Haerkens J, van der Maden MME, Hruba E, Veerman D, Bufe A, Almedawar S, van der Meer AD, Barta T, Collin RWJ, Garanto A. Long-term daily light exposure boosts human retinal organoid differentiation. Communications Biology. DOI: 10.1038/s42003-026-10216-w
Celiker C, Hruba E, Kyriakou K, Dorgau B, Molina Gambin F, Weissova K, van Oosten E, Englmaier L, Vaskovicova N, Savage MA, Hilgen G, Sernagor E, Garanto A, Lako M, Barta T. Photostimulation Improves Maturation of Human Photoreceptors. Nature Communications. DOI: 10.1038/s41467-026-76112-3
