ResearchIn-Press PreviewNeuroscienceOphthalmology
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10.1172/jci.insight.197880
1Department of Orthopedics, University of Electronic Science and Technology of China, Chengdu, China
2The Sichuan Provincial Key Laboratory for Human Disease Gene Study and Cent, University of Electronic Science and Technology of China, Chengdu, China
3Beijing Chinagene Co., Beijing, China
4Department of Ophthalmology, Peking University, Beijing, China
Find articles by Liu, W. in: PubMed | Google Scholar
1Department of Orthopedics, University of Electronic Science and Technology of China, Chengdu, China
2The Sichuan Provincial Key Laboratory for Human Disease Gene Study and Cent, University of Electronic Science and Technology of China, Chengdu, China
3Beijing Chinagene Co., Beijing, China
4Department of Ophthalmology, Peking University, Beijing, China
Find articles by Wu, X. in: PubMed | Google Scholar
1Department of Orthopedics, University of Electronic Science and Technology of China, Chengdu, China
2The Sichuan Provincial Key Laboratory for Human Disease Gene Study and Cent, University of Electronic Science and Technology of China, Chengdu, China
3Beijing Chinagene Co., Beijing, China
4Department of Ophthalmology, Peking University, Beijing, China
Find articles by Zou, R. in: PubMed | Google Scholar
1Department of Orthopedics, University of Electronic Science and Technology of China, Chengdu, China
2The Sichuan Provincial Key Laboratory for Human Disease Gene Study and Cent, University of Electronic Science and Technology of China, Chengdu, China
3Beijing Chinagene Co., Beijing, China
4Department of Ophthalmology, Peking University, Beijing, China
Find articles by Zhang, F. in: PubMed | Google Scholar
1Department of Orthopedics, University of Electronic Science and Technology of China, Chengdu, China
2The Sichuan Provincial Key Laboratory for Human Disease Gene Study and Cent, University of Electronic Science and Technology of China, Chengdu, China
3Beijing Chinagene Co., Beijing, China
4Department of Ophthalmology, Peking University, Beijing, China
Find articles by Fan, Y. in: PubMed | Google Scholar
1Department of Orthopedics, University of Electronic Science and Technology of China, Chengdu, China
2The Sichuan Provincial Key Laboratory for Human Disease Gene Study and Cent, University of Electronic Science and Technology of China, Chengdu, China
3Beijing Chinagene Co., Beijing, China
4Department of Ophthalmology, Peking University, Beijing, China
Find articles by Sun, K. in: PubMed | Google Scholar
1Department of Orthopedics, University of Electronic Science and Technology of China, Chengdu, China
2The Sichuan Provincial Key Laboratory for Human Disease Gene Study and Cent, University of Electronic Science and Technology of China, Chengdu, China
3Beijing Chinagene Co., Beijing, China
4Department of Ophthalmology, Peking University, Beijing, China
Find articles by Yang, L. in: PubMed | Google Scholar
1Department of Orthopedics, University of Electronic Science and Technology of China, Chengdu, China
2The Sichuan Provincial Key Laboratory for Human Disease Gene Study and Cent, University of Electronic Science and Technology of China, Chengdu, China
3Beijing Chinagene Co., Beijing, China
4Department of Ophthalmology, Peking University, Beijing, China
Find articles by Hu, J. in: PubMed | Google Scholar
1Department of Orthopedics, University of Electronic Science and Technology of China, Chengdu, China
2The Sichuan Provincial Key Laboratory for Human Disease Gene Study and Cent, University of Electronic Science and Technology of China, Chengdu, China
3Beijing Chinagene Co., Beijing, China
4Department of Ophthalmology, Peking University, Beijing, China
Find articles by Zhang, L. in: PubMed | Google Scholar
1Department of Orthopedics, University of Electronic Science and Technology of China, Chengdu, China
2The Sichuan Provincial Key Laboratory for Human Disease Gene Study and Cent, University of Electronic Science and Technology of China, Chengdu, China
3Beijing Chinagene Co., Beijing, China
4Department of Ophthalmology, Peking University, Beijing, China
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Zhu, X.
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Published March 20, 2026 - More info
N6-methyladenosine (m6A) modification is the most prevalent post-transcriptional epigenetic modification in mammalian mRNAs, and it has been implicated in the regulation of nervous system development by modulating mRNA metabolism. VIRMA is the largest core subunit of the m6A methyltransferase complex and essential for the assembly and stability of the m6A methyltransferase complex. In the retina, m6A methylation modification is widely distributed in various cellular layers and is essential for retinal homeostasis. Here, we demonstrate that VIRMA-mediated m6A modification is essential for retinal homeostasis. Loss of Virma in retinal rod cells resulted in abnormal reduction in m6A methylation levels, along with impaired photoreceptor function and degeneration. Mechanically, Virma depletion in photoreceptors dampened the m6A modification level of visual perception-associated genes, resulting compromised visual function and photoreceptors degeneration. Moreover, Virma interacts with splicing factor to regulate the alternative splicing events of retina function-related genes such as Polg2, which contributes to photoreceptor damage. Reintroduction of normal Virma expression colonially rescued photoreceptor degeneration. Collectively, our data elucidate the important role of Virma-mediated m6A modification in photoreceptor function and suggest that epigenetic modulation could serve as potential targets to treat these blinding diseases.