A transcriptomic analysis to identify 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

Scientists know the sequence of events that occur in fovea development during pregnancy and after birth. However, less is known about the individual molecules involved, and why the fovea doesn’t develop properly in some people.

This project will use another animal that has sharp colour vision – the zebrafish. Zebrafish have a region in the retina called the high acuity area (HAA) that is similar to the fovea. This project will study genes involved in development of the HAA in intricate detail.

Aim of the research project

This project aims to identify genes involved in healthy HAA development and compare these to gene activity when the HAA does not develop properly. This will reveal genes that could be important in development of the fovea in humans.

Key procedures/objectives

1. Analyse the activity of genes in three types of zebrafish: 1) healthy zebrafish with normal HAA, 2) zebrafish with a mutation that prevents healthy HAA development, and 3) fish with a mutation that causes overdevelopment of the HAA.
2. Analyse gene activity at two timepoints: early in the onset of HAA development (equivalent to embryo development in humans) and a later stage when the HAA is well established (corresponding to development after birth in children).
3. Compare the gene activity in the three zebrafish and both timepoints to identify which genes are important for healthy HAA formation.

Potential impact on people with sight loss

If successful, this project will provide a list of candidate genes and cell pathways, whose human equivalents could be involved in fovea development. It’s an essential first step in understanding the cellular pathways involved in human fovea development and how they might go wrong in some people.