(Press-News.org)
Ikoma, Japan—The retina is a thin layer of neural tissue at the back of the eye that detects light and converts it into signals, sent to the brain. During development, all the specialized neurons in the retina—including photoreceptors and other cells essential for vision—arise from stem-like cells known as retinal progenitor cells (RPCs). Although RPCs can differentiate into multiple retinal cell types, this capacity is only temporary in mammals. As development proceeds, RPCs gradually lose their flexibility and ultimately transform into supporting cells called Müller glia (MG). Once this transition is complete, the retina has no ability to regenerate lost neurons, even when damaged.
As populations worldwide age, retinal diseases are becoming increasingly prevalent. Scientists have tried to understand how RPCs maintain their identity during development before they lose it, hoping to use these insights to develop regenerative therapies. Studies have pointed to epigenetic regulation—chemical modifications to DNA and associated proteins that influence gene activity—as a key factor. Particularly, changes in chromatin, the DNA–protein complex that packages genetic material, are known to affect whether genes are accessible for protein expression. However, the precise epigenetic mechanisms that distinguish RPCs from MG at the chromatin level remain unclear.
To fill this gap, a research team led by Associate Professor Taito Matsuda from the Nara Institute of Science and Technology (NAIST), Japan, conducted a detailed molecular study on developing mouse retinas. Their work, made available online on January 29, 2026, and published in Volume 21, Issue 2 of Stem Cell Reports on February 10, 2026, was co-authored by Dr. Kanae Matsuda from NAIST, Dr. Haruka Sekiryu, Professor Koh-Hei Sonoda, Associate Professor Yusuke Murakami, and Professor Kinichi Nakashima, all from Kyushu University, Japan.
The researchers first isolated mouse RPCs at different stages of development and analyzed both gene expression and chromatin accessibility using genome-wide sequencing approaches. These analyses pointed to Setd8—an enzyme that modifies structural proteins around which DNA is wrapped—as a key player in preserving the progenitor state in RPCs.
Through experiments in genetically engineered mice, the researchers showed that developing RPCs lacking Setd8 exhibited reduced proliferation, increased DNA damage, and higher cell death. As a result, the retina became thinner, and fewer later-developing neurons were produced. Further analysis revealed that loss of Setd8 led to widespread closing of chromatin regions that are normally open in RPCs, resulting in downregulation of genes involved in maintaining progenitor identity and DNA repair. “These insights are relevant to regenerative medicine and ophthalmology, where understanding and manipulating epigenetic mechanisms could contribute to the development of novel therapeutic strategies for vision restoration,” remarks Matsuda.
By identifying an enzyme that helps keep RPCs in their flexible, stem cell-like state, the study highlights a potential target for future approaches aimed at repairing damaged retinas. “Our laboratory focuses on cellular reprogramming that can flexibly alter cell fate, so we are happy about the clarified part of the mechanism that supports retinal progenitor identity. Future research will aid in achieving newer regeneration therapies,” concludes Matsuda.
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Resource
Title: Histone methyltransferase Setd8 preserves chromatin accessibility to safeguard retinal progenitor cell identity during development
Authors: Haruka Sekiryu, Sakurako Shimokawa, Kanae Matsuda-Ito, Hisanobu Oda, Yusuke Murakami, Koh-Hei Sonoda, Kinichi Nakashima, and Taito Matsuda
Journal: Stem Cell Reports
DOI: 10.1016/j.stemcr.2025.102789
Information about the Laboratory of Neural Regeneration and Brain Repair can be found at the following website: https://bsw3.naist.jp/matsuda/
About Nara Institute of Science and Technology (NAIST)
Established in 1991, Nara Institute of Science and Technology (NAIST) is a national university located in Kansai Science City, Japan. In 2018, NAIST underwent an organizational transformation to promote and continue interdisciplinary research in the fields of biological sciences, materials science, and information science. Known as one of the most prestigious research institutions in Japan, NAIST lays a strong emphasis on integrated research and collaborative co-creation with diverse stakeholders. NAIST envisions conducting cutting-edge research in frontier areas and training students to become tomorrow's leaders in science and technology.
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