Newly discovered gene mutation in eye disease named after blind Irish poet.

Researchers in University College Dublin (UCD) led by Professor Breandan Kennedy have discovered that a mutation in a gene called emc1 causes major vision problems in zebrafish.

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 Irish poet Antoine Ó Raifteirí. Zebrafish with this mutation had poorly developed eye cells, weaker responses to light, and changes in the normal structure of their retinas. 

Describing the key findings of the study, postdoctoral researcher in the Kennedy group, 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.”

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. 

“Our research shows the vital role of Emc1 in vision and lays the groundwork for exploring potential solutions to its dysfunction.”

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. Over 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 behaviour in the absence of this gene and discover that photoreceptors are particularly sensitive to loss of emc1", explains Dr McCann.

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.

 Mise Raifteirí, an file,
lán dóchais is grá
le súile gan solas,
ciúineas gan crá

I am Raifteirí, the poet,
full of hope and love
With eyes without light,
silence without torment.

Journal Reference     

McCann, Tess et al. “Emc1 is essential for vision and zebrafish photoreceptor outer segment morphogenesis.” FASEB journal : official publication of the Federation of American Societies for Experimental Biology vol. 38,19 (2024): e70086. doi:10.1096/fj.202401977R

Antoine Ó Raifteirí was an 18^th Irish language poet who lost his vision following an illness in childhood. The first four lines of his poem, "Mise Raifteirí an File" appeared on the reverse of the Irish five pound note (Series C).