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University College Dublin researchers uncover vital insights into inherited blindness through zebrafish model.
In a breakthrough study, researchers at University College Dublin (UCD) have identified a mutation in the emc1 gene that causes severe vision problems in zebrafish. The discovery has been named the “raifteirí” (raf) mutation, after the 18th-century blind Irish poet Antoine Ó Raifteirí, reflecting Ireland’s cultural heritage. The findings, published in The FASEB Journal, shed light on the mechanisms of inherited retinal diseases and hold promise for future treatments.
The team behind the study used zebrafish as a model to investigate inherited blindness. By creating random mutations across the zebrafish genome and screening their offspring for visual impairments, they identified the emc1 mutation. Zebrafish carrying this mutation exhibited significant defects: poorly developed eye cells, weak responses to light, and abnormal retinal structures.
The Importance of Emc1
Dr. Tess McCann, a postdoctoral researcher at UCD, explained the findings:
“The raf zebrafish didn’t react to visual tests and had major vision problems. The eye cells in these zebrafish were thinner and had unusual shapes. Genes needed to help the eye process light signals weren’t working as they should. Our research shows the vital role of Emc1 in vision and lays the groundwork for exploring potential solutions to its dysfunction.”
The emc1 gene plays a critical role in the function of the endoplasmic reticulum, a cellular structure responsible for protein production and transport. Mutations in this gene disrupt the proper functioning of retinal cells, leading to degeneration and progressive vision loss—a hallmark of inherited retinal diseases.
Zebrafish as a Tool for Eye Disease Research
Zebrafish are a valuable model for studying human diseases due to their genetic similarities to humans. The research team developed the first vertebrate model with a complete loss of the emc1 gene, allowing for a detailed assessment of visual behavior and the effects of this gene’s absence on photoreceptors.
“Photoreceptors are particularly sensitive to the loss of emc1,” said Professor Breandan Kennedy, from the UCD School of Biomolecular & Biomedical Science and UCD Conway Institute. “This model gives us a powerful tool to study EMC-related human diseases and explore therapeutic approaches.”
Hope for Future Treatments
Inherited retinal diseases, caused by mutations in more than 300 known genes, currently have limited treatment options. Only one approved therapy exists, and it is suitable for a small subset of patients. The new findings offer hope for developing treatments that target emc1-related conditions.
Professor Kennedy highlighted the next steps for the research:
“We now have opportunities to investigate the potential effects of emc1 gene mutations linked to human patients but not yet experimentally confirmed. We can also test pharmacological compounds previously identified by our team to determine if vision can be restored.”
The Significance of “Raifteirí”
The decision to name the mutation “raifteirí” emphasizes the connection between scientific discovery and cultural identity. It underscores a hopeful outlook for future advances in treating inherited blindness, with the name serving as a tribute to Antoine Ó Raifteirí’s resilience and legacy.
The study marks a significant advance in understanding the genetic underpinnings of blindness and paves the way for innovative therapeutic strategies to combat these rare and devastating eye conditions.
Reference:
Tess McCann et al., Emc1 is essential for vision and zebrafish photoreceptor outer segment morphogenesis, The FASEB Journal (2024). DOI: 10.1096/fj.202401977R
