Killifish: a faster way to study retinal ageing 

Studies on the ageing eye, including genetic studies, are challenging due to the limited experimental models available to researchers. This ultimately slows down research into why we lose sight as we age and impacts the development of new therapies to combat age-related vision decline and disease.

The retina is the thin layer at the back of the eye made up of different types of neural cells and support cells called glia. These cells function together to detect light and transmit the signal to the brain where it is converted to the image that we see. 

The structure and function of the healthy human retina degrades with age and relatively little is known about the biology of ageing processes in the eye. 

Ageing is the most significant risk factor for retinal degeneration, increasing the susceptibility to diseases, such as age-related macular degeneration or glaucoma. 

Hallmarks of the ageing retina include tissue thinning, neuronal loss and reduced visual function.

Retinal degeneration often progresses over months or years, whereby neurons gradually die leading to dysfunction, vision loss, and reduced quality of life.

It is essential that we identify the mechanisms for why the retina breaks down with age, so we can design new therapies to correct them and ultimately slow, stop or reverse sight loss. 

The African turquoise killifish (Nothobranchius furzeri) is a freshwater fish that lives 4 to 6 months, which is the shortest known lifespan of any animal with a backbone.

In comparison, the lifespan of zebrafish, a widely used model organism in eye research, is around 3 years, which makes it a challenging and expensive model in which to study ageing processes.

The killifish also has an eye structure similar to human eye and shows common signs of ageing including vision loss and neurodegeneration.

The potential to study the rapidly ageing killifish could significantly advance discoveries and our understanding of why we age and how we can slow or reverse damage in the ageing eye.

Dr Ryan MacDonald proposes to establish the African turquoise killifish (Nothobranchius furzeri), as a new model to study retinal ageing. The killifish retina is similar to structure and function of the human but has an added advantage that it ages rapidly in 4-6 months. 

Dr MacDonald and team have expertise in developing, imaging and studying fish models of human neurodegenerative disease. They are well-positioned to establish the killifish as a rapidly ageing model to study age-related neurodegenerative disease mechanisms in the retina. 

The aims of this project are to investigate whether the aged killifish retina shows similar signs of retinal degeneration as are found in aged human retina; and whether the molecular processes driving neurodegeneration are the same for humans and fish.

Killifish could provide a new and unique opportunity to understand ageing processes in the retina. 

Dr MacDonald and team will then be able to modify gene expression in specific cell populations in the killifish retina to investigate the roles of individual genes in protection or degeneration of the ageing retina.

This research could significantly contribute to our understanding of precise mechanisms as to why retinal degeneration is exacerbated with age. This could be an essential step towards designing targeted therapies to slow down or prevent retinal degeneration, and combat vision decline with age.

During this PhD project, Ola Krzywanska will be expertly trained in cellular and molecular biology, and data analysis. Thereby, setting her up for a promising career in scientific research to explore and develop new therapies for human disease.