Researchers at University College Dublin (UCD) have discovered that a mutation in a gene called emc1 causes major vision problems in zebrafish. Zebrafish with this mutation had poorly developed eye cells, weaker responses to light, and changes in the normal structure of their retinas. These tiny, tropical fish are used as a tool to find novel genes that cause inherited blindness and help find better treatments for inherited retinal blindness.

The team artificially created mutations randomly across the genome of the zebrafish. The offspring of these zebrafish were then screened for the characteristics of blindness. One of the zebrafish families identified by the team carries a mutation in the emc1 gene, which they are initially calling the “raifteirí” (raf) zebrafish after the 18th-century blind Irish poet Antoine Ó Raifteirí. The findings are published in The FASEB Journal.

Postdoctoral researcher Dr. Tess McCann explains, “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 is crucial for the proper functioning of the endoplasmic reticulum, which is a part of the cell involved in protein production and transport. This study highlights the role of emc1 gene in retinal health and provides insights into how mutations in this gene can lead to inherited retinal diseases.

Inherited retinal diseases are rare eye conditions that lead to progressive vision loss due to the degeneration of cells in the retina, the light-sensitive layer at the back of the eye. More than 300 genes have been identified in patients but it is often unclear how the mutations cause sight loss.

Currently, there is one approved therapy but this is only suitable for use in a small number of patients. There is no effective treatment available for many patients.

The research also shows how zebrafish is a valuable tool for studying human diseases and finding new treatments because they share many biological similarities with us.

“We have developed the first vertebrate animal model with total loss of emc1. This is an extremely useful tool for studying eye diseases and finding new treatments. It enabled us to perform the first comprehensive assessment of visual behavior in the absence of this gene and discover that photoreceptors are particularly sensitive to loss of emc1.”

Professor Breandan Kennedy and his team are planning further research with this new zebrafish model to understand EMC-related human disease and help discover therapeutic approaches.

Professor Kennedy from UCD School of Biomolecular & Biomedical Science and UCD Conway Institute said, “We now have opportunities to investigate the potential effects of emc1 gene mutations that have been linked to human patients but have yet to be experimentally confirmed. We can also use pharmacological compounds identified previously by our team to see if vision can be restored.”

The guidelines for naming genes include conveying something about the character or function of the gene product. Raifteirí (raf) draws on Irish heritage and highlights the cultural identity in scientific naming. It implies reason to be lán dúchais (full of hope) for future treatments in inherited blindness.