Identification of novel genes involved in fovea formation

Brief Lay background

Our ability to see in sharp colour vision is down to a structure in the middle of the retina called the fovea. In some people, the fovea doesn’t develop properly and this can cause severe vision problems that impact on quality of life. This is called foveal hypoplasia.

Foveal hypoplasia sometimes occurs alongside other structural defects in the eye, but it’s thought that around 3% of children with normal vision also have the condition.

What problem/knowledge gap does it help address

Although birth defects are likely to be caused by faults (mutations) in genes, many cases of foveal hypoplasia lack a genetic diagnosis. Without this, a clinician may not be able to provide the most optimal management.

Genetic diagnosis relies on identifying genes involved in the condition and their role – in this case, genes involved in fovea formation. Zebrafish have an area in their retina specialised in high acuity vision – similar to the fovea – making them a good model organism for research.

By comparing the genes that are turned on in the retina of a fish which contains a known genetic fault with those genes turned on in wild type zebrafish, the team have identified a subset of genes that may be important for the formation and function of the zebrafish high acuity area.

Aim of the project

To characterise the function of genes affected in zebrafish without a high acuity area.

This award will also contribute to building capacity in eye research as it will lead to a PhD for an early career researcher.

Key procedures/objectives

The PhD student will:

1. Perform comparative analyses of gene expression in zebrafish with and without a high acuity area.
2. Determine the specific function of three genes during high acuity area formation in zebrafish.
3. Work with clinical and computational genetics collaborators to identify other potential gene variants.

Potential impact on people with sight loss

Identifying genes involved in the formation of the high acuity area in the zebrafish could potentially reflect those involved in fovea formation in humans. Understanding how these genes work, and which are relevant, could be the first step towards a diagnostic panel.