Grace Ruddin is based at UCD and is an IRC Enterprise Partnership Scheme Postgraduate Scholar.
Project: Investigating the biology of the inherited human blindness gene RGR-opsin
Start date: September 2023
Award amount: This project is co-funded between Fighting Blindness and IRC, Fighting Blindness is contributing €27,000 towards the project.
The overall aim of the project is to develop an understanding of an inherited retinal degeneration (IRD) gene and its association with inherited blindness. Zebrafish models will be used to understand the biology of the gene which codes for a protein called retinal G protein coupled receptor (RGR)-opsin. Zebrafish are small tropical fish and the structure of the zebrafish retina is similar to the human retina.
Within the retina, there are various layers and cells. Photoreceptors and retinal pigment epithelium (RPE) cells are examples of these. Rod and cone photoreceptors and RPE cells die or become dysfunctional as a result of IRDs. Cone photoreceptors are involved in photopic vision (eye vision under well-lit conditions), which is a poorly understood process. As zebrafish display cone-dependent vision, they will be used to study this process. The retina must recycle a light sensitive form of vitamin A to sustain vision. RGR-opsin is thought to be involved in this process. Zebrafish models will be used to determine if this IRD gene of interest is involved in photopic vision.
Zebrafish knockout models, where a gene has been inactivated in the zebrafish, can be used to understand the function of RGR-opsin but not missense mutations of the protein. A missense mutation is a change in a single letter of the DNA code for a gene. Missense mutations in RGR-opsin are associated with retinitis pigmentosa, a prevalent form of IRD. There is a lack of knowledge regarding if and how RGR gene mutations cause vision loss, as well as which gene variants are pathogenic (disease causing). Transgenic zebrafish will be generated in this project, through which the zebrafish will be genetically altered to express patient RGR variants. This is to identify which poorly understood mutations (variants of unknown significance) are disease causing and to gain a better understanding of how mutations in RGR-opsin cause vision loss.
I completed my final year BSc Neuroscience research project using zebrafish to model a different IRD gene in Professor Kennedy’s laboratory. By conducting this research and by working as an administrator in an eye centre during my summer holidays informed me how broad ophthalmology is and how much remains unknown. IRDs can impact a person’s mobility and independence. I decided to pursue a PhD in vision research in the hope that I can potentially make a positive difference to someone’s life.
I really enjoy that there are different aspects to the project such as working with zebrafish and being involved in Public Patient Involvement (PPI). I enjoy working alongside the talented and motivated researchers within the Kennedy group.
Researchers in the Kennedy group also study uveal melanoma, a rare type of cancer which develops in the eye. It is intriguing to listen about their research because they use differential experimental approaches. Their research focuses on drug testing on patient samples.
Following the completion of her BSc Neuroscience degree, Grace decided to pursue a PhD in vision research. In September 2023 she commenced her PhD in the Kennedy lab at the UCD Conway Institute. Apart from research she enjoys playing the harp and going on walks with her dog Marley!
I am very fortunate that the Irish Research Council and Fighting Blindness are funding my research. The overall aim of my project is to use zebrafish models to develop an understanding of IRDs. – Grace Ruddin
Click below to listen to what Grace had to say about the event: