Investigating the genetics of keratoconus
Professor Alison Hardcastle | GR001304
26 July 2021
A new PhD studentship, supervised by Professor Alison Hardcastle at UCL Institute of Ophthalmology, will use genetics to increase our understanding of the causes of keratoconus. The ultimate aim is to inform the development of genetic tests and therapies for patients.
Keratoconus is an eye condition that will usually present in adolescents and young adults. This condition therefore impacts people at an age when any change in vision can have a considerable effect on quality of life and employment opportunities.
What is keratoconus?
Keratoconus is a non-inflammatory eye condition. It causes the cornea, the round dome-shaped clear window of the eye, to progressively thin forming a cone-like bulge. This eventually impairs the ability of the eye to focus properly, potentially causing poor vision.
- It is usually diagnosed in young people in their late teens or early twenties
- The exact cause remains unknown but genetics and environmental factors are believed to play a role
- It is more common in non-Caucasian populations
- At early stages of the condition, glasses or contact lenses may be used to correct vision
- In very advanced cases a corneal transplant may be needed
If the keratoconus is not detected early enough, patients may require a cornea transplant and, if it remains untreated, it can lead to blindness. However, little is known about the causes of keratoconus and detecting disease early enough to prevent loss of vision remains a challenge.
Finding a solution
Recent research has shown that genetics play a major role in causing keratoconus, but scientists have yet to find the exact genes involved. This PhD studentship will analyse keratoconus genetic sequences using cutting-edge techniques to pinpoint genetic changes in patients.
Professor Hardcastle and colleagues have sequenced DNA from thousands of Moorfields Eye Hospital patients who have kindly donated a DNA sample. Additionally, in some cases corneal tissue was also donated when patients had a cornea transplant. Using these invaluable samples, a previous genome-wide association study (GWAS) from the team identified several key genetic risk factors in keratoconus patients.
However, the researchers also need to detect the more rare genetic variants, which wouldn’t have been picked up in the GWAS analysis.
In this new project, the student will use a number of techniques, including whole genome sequencing (WGS) to detect these rare genetic variants in keratoconus patients. They will then look at how these mutations impact gene expression and the molecular pathways in the cell to understand the underlying causes of keratoconus.
Hear from Professor Alison Hardcastle
Professor Alison Hardcastle discusses the exciting potential of using a combination of genetics and cell biology to help diagnose patients and test therapies at the UCL Institute of Ophthalmology.
By identifying novel DNA changes and the genes involved in causing keratoconus, this study could inform the development of a genetic test to identify individuals at risk of keratoconus. Therefore, it has the potential to inform earlier diagnosis, thereby improving patient care and preventing vision loss.
Moreover, knowledge of the genes and pathways involved in causing the characteristic conical distortion of the cornea in keratoconus patients could ultimately lead to the development of new treatments.
Professor Alison Hardcastle
Genetics/inherited eye disorders, corneal/ocular surface disease