From Zebrafish to human eyes: Investigating the RGR protein and its link to vision loss

An exciting scientific review by our funded researchers at University College Dublin explores 30 years of research into the role of the RGR protein in vision loss, and its potential as a target for future treatments.

 

We had the opportunity to talk with Grace Ruddin, PhD student at UCD Conway Institute and first author of the article ‘The dark and bright sides of retinal G protein-coupled receptor (RGR) in vision and disease’ about the aims of this research and how it could benefit those affected by sight loss. This scientific review article came out of a project led by Prof. Kennedy, UCD, in part funded by Fighting Blindness.

What are the overall aims of this research?

The overall aim of this review article was to provide a detailed overview of the role of the RGR protein (G protein-coupled receptor) in vision, its association with ocular disease and role in non-ocular function and disease.

RGR is a protein located in the eye. Changes in the function or expression of RGR are linked with retinal diseases such as Inherited Retinal Degeneration (IRD) and Age-related Macular Degeneration (AMD).

In this study,  RGR protein acts as an additional molecular mechanism in the eye  which enables vision by producing a light sensitive form of vitamin A known as 11-cis-retinal (11cRAL). This form of vitamin A is used by the light detecting cells in the eye, called photoreceptors, to enable vision – particularly during bright light conditions.

How could it have an impact on those affected by sight loss?

Through writing the review, it became apparent that there are discrepancies in the literature regarding the role of RGR. We acknowledged these differences and highlighted knowledge gaps.

We are in the process of investigating some of the knowledge gaps using Zebrafish, a small tropical fish. While zebrafish are used a lot in vision research, given that the structure of the zebrafish and human eye are similar, it has not been used to understand RGR.

We studied the rgr gene which is responsible for the production of the RGR protein. In our zebrafish models, this gene has been genetically inactivated (knockout models) to determine if the loss of the RGR protein affects vision. As this gene is associated with IRDs and AMD, I hope to develop a better understanding of the role of RGR in vision and disease.

Given that there are currently no approved treatments for individuals with RGR-specific ocular disorders, future research will focus on the therapeutic potential of drugs to rescue visual cycle defects. Through this and by understanding the role of RGR, I hope my research will benefit those affected by sight loss.

 

Thank you to all the researchers who worked on this study! 

Grace Ruddin, Tess McCann, John D. Fehilly, Jodie Kearney, and Prof. Breandán N Kennedy, UCD School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, Dublin, Ireland.

Sources 

• Click here to find the full information about the publication.
• Grace Ruddin was previously awarded a Postgraduate Scholarship through the Irish Research Council’s (IRC) Enterprise Partnership Scheme for her research on the RGR protein. The scholarship was co-funded by the IRC and Fighting Blindness, which served as the enterprise partner. You can learn more about Grace’s work on the RGR protein here.