Novel models to study retinal vascular disease
Dr Ryan MacDonald | GR001208
17 December 2021
The retina, the light sensitive part of your eye, is critically important for vision. It uses a lot of energy and generates significant amount of metabolic waste that needs to be removed. For this, the eye has a specialised maintenance system – the retinal neurovascular unit. It works to ensure the optimal performance of the retina.
Based at the UCL Institute of Ophthalmology, Dr Ryan MacDonald and Dr Elisabeth Kugler are funded through a Springboard award to generate an image-based computational model of retinal neurovascular unit development and function in health and disease.
The retinal neurovascular unit (NVU) is made up of neurons, blood vessels (visualised as magenta cells on the image above) and dedicated support cells called glia (blue cells). These different types of cells come together during eye development and go onto support the retina throughout life. This system is known to break down in disease, such as diabetic retinopathy. Without it, the retina cannot function properly and starts to degenerate, leading to vision loss.
Finding a solution
In this project Ryan and the team hope to address important questions:
- How is the NVU built and organised on a cellular level?
- When does it become functional?
- How does it interact with the rest of the retina?
To address these questions, the team will use zebrafish, as their retina is structurally similar to the human retina. Furthermore, the eye development in zebrafish can be observed in real time and at single cell resolution using advanced microscopy and computer analyses.
This advanced live imaging will be the basis for creating models of NVU development and function.
The novel models generated in this project will provide new insight into the development of the retina and how it is cared for in health and disease. When applied to different disease scenarios, it is hoped that these models will help to identify key pathogenic processes involving the NVU.
This is critically important, as current medical diagnostics tools cannot tell the details of when, how and which cell types are affected in different diseases that cause sight impairment and loss. Ultimately, it could enable the identification of novel therapeutic targets.
The neurovascular unit is a complex structure, critical for the health and maintenance of your eye throughout life. It often breaks down in disease leading to sight loss. With support of this Springboard Award, we will tackle the questions of how and why this degeneration occurs.
Dr Ryan MacDonald
Dr Ryan MacDonald
Macular degeneration), Diabetic retinopathy„ Retinal/vitreo-retinal