Landmark genetic study sheds new light on how the eye develops its sharpest vision

Combining artificial intelligence and genetics has allowed researchers to study the part of the eye that gives us sharp central vision in amazing detail for the first time. 

Researchers from the University of Leicester, University Hospitals of Leicester Trust through the Ulverscroft Eye Unit, together with international collaborators, carried out the first ever genome-wide study of human foveal development – the tiny pit at the back of the eye that gives us sharp central vision for reading, recognising faces, and driving. 

Results of the study, which was funded by the Wellcome Trust, Ulverscroft Foundation and National Institute for Health and Care Research (NIHR) Leicester Biomedical Research Centre (BRC) among others, have just been published in Investigative Ophthalmology & Visual Science.

Using advanced artificial intelligence to analyse eye scans from over 60,000 UK Biobank participants, the team identified more than 120 genetic signals that shape how the fovea develops. Remarkably, they discovered 64 genes never before linked to the fovea, including pathways involved in vitamin A metabolism, retinal cell fate, vascular development, and pigmentation.

The study shows that both common and rare genetic variants influence whether the fovea forms normally, helping explain why conditions such as albinism, aniridia, and other genetic syndromes cause foveal underdevelopment and lifelong vision problems. 

Importantly, the team also demonstrated that foveal abnormalities are present in systemic diseases such as Stickler syndrome, Refsum disease, Leber congenital amaurosis with early-onset deafness, and microcephaly–chorioretinopathy syndromes, extending the clinical impact far beyond the eye.

This landmark work provides the first genetic map of foveal formation and suggests a continuum model of eye development, where both subtle genetic variation and rare mutations can affect visual outcomes. 

Dr Mervyn Thomas, Clinical Associate Professor, Honorary Consultant Ophthalmologist and Clinical Lead at the Ulverscroft Eye Unit at the University of Leicester, led the study.

He said: “The findings provide the first comprehensive genetic dissection of human foveal pit architecture, revealing entirely new biological mechanisms that shape foveal development and extending our understanding of childhood visual disorders. 

“We now know that foveal development is affected in Refsum disease, Stickler Syndrome and Leber congenital amaurosis. Our data also highlights the role of retinoic acid (vitamin A derivative) signalling in human foveal development – something previously unknown.

“These discoveries fundamentally change our understanding of how the back of the eye develops and open up new avenues for diagnosing and treating childhood vision loss.”

The research was made possible through the generosity of more than half a million UK Biobank volunteers, who contributed their health data to enable discoveries of this scale.

The study was a true international collaboration, with major contributions from early-career researchers. Among them, Callum Hunt, a Wellcome Trust PhD student at the University of Leicester, who led much of the analysis that made these discoveries possible.

Dr Thomas added: “This was truly a team effort across Leicester, Moorfields, UCL, King’s College London, Baylor, Cornell, UC Irvine, UC Davis, and other centres. It shows the power of collaboration and the importance of supporting young scientists. Above all, we are grateful to the UK Biobank participants, without whom this work would not have been possible.”