Modelling degenerative diseases of the retina
Dr Ryan MacDonald | GR001148
15 October 2020
Retinal degenerative diseases are a leading cause of sight loss in developed countries. This includes macular disease - the biggest cause of sight loss in the UK.
We are funding a PhD studentship to generate novel zebrafish models of retina degeneration and to study neuronal cell loss and dysfunction in the context of specific disease-associated mutations.
The retina is the light-sensitive tissue lining the back of our eye. It is made of two cell types, neurons and supporting cells, glia, that connect to each other to make circuits required for vision.
Retinal degenerative disorders are diseases where the retina breaks down resulting in sight loss. It is currently unknown why this happens and there are few treatments.
Finding a solution
Matrix Metalloproteinases (MMPs) are important molecules for the healthy development of the retina. The genes coding for MMPs are associated with several retinal degenerative diseases supporting the theory for their role in healthy visual development.
In this project, the PhD student will use CRISPR-Cas9 based genome modification to generate mutants or “avatars” in MMPs genes which are patient specific. These avatars will help determine the role of the MMP genes in retina degeneration and dysfunction. This approach will enable the team to visualise and characterise degenerative mechanisms in the retina.
Hear from Dr Ryan MacDonald
Dr Ryan MacDonald talks about the exciting potential of the zebrafish model for their goal of finding new therapies for patients with sight loss. He explains how the zebrafish allow researchers to see eye development happen in real time and are helping them to better understand how genetic mutations can cause vision loss.
This project will identify fundamental cellular and molecular mechanisms underlying neuronal loss and dysfunction in retinal degenerative disorders such as age related macular degeneration.
These mechanisms could provide new insight into how and why the retina degenerates. This work will also validate using zebrafish avatars to better understand human retinal disease. These avatars can then be used in follow up studies to determine the role of MMPs in age related degenerations and for drug screening or validation of gene therapies to treat these debilitating retinal diseases.
Dr Ryan MacDonald
Macular degeneration, Diabetic retinopathy, Genetics/inherited eye disorders