Finding the genetic cause of a type of keratoconus that’s inherited

Research details

  • Type of funding: PhD Studentship
  • Grant Holder: Professor Chris Inglehearn
  • Institute: University of Leeds
  • Region: Yorkshire and the Humber
  • Start date: January 2012
  • End Date: December 2014
  • Priority:
  • Eye Category:


Keratoconus is a condition in which the clear front surface of the eye (the cornea) thins and changes shape. About 1 in 2000 people are affected worldwide. In severe cases, people will need transplant surgery to replace the cornea with a healthy one from a donor.

It is often a lifelong illness and, while treatments are available, they carry risks and are not always successful. So there is a real need for new and better treatments, but developing them is held back by not knowing enough about what causes the condition.

In this project the student is using genetics to study keratoconus in families where the condition is passed on recessively. This type of inheritance means that you need 2 faulty versions of a gene (one from each parent) in order to be affected by the condition. If you have only 1 faulty copy, the healthy copy is usually enough to compensate, but you can still pass on the faulty copy to your children.

The student is trying to find matching sections of DNA in family-members who are affected by the condition in order to pinpoint the genes involved. Once the genes have been found, the student can test to find out which ones are active in the cornea, both in healthy eyes and in keratoconus, and can study the proteins the genes produce to find out what they’re doing.

Results from the study will mean that clinicians can give a clearer picture of likely risks and outcomes to patients and their families. They will also allow ophthalmologists to work out how successful different treatments might be for different subtypes of keratoconus and will help in the search for new treatments.
  • Scientific summary

    Determining the genetic basis of keratoconus and implications for treatment

    Keratoconus (KC) is a bilateral, progressive corneal ectasia affecting around 1 in 2000 people. It is the leading cause of corneal transplants, but its pathology is poorly understood. Genetics offers a hypothesis-independent route to identify the defective proteins and pathways involved. KC genetic studies to date have concentrated primarily on large dominant families, but epidemiological evidence points to a major contribution from recessive alleles. The aim of this studentship is therefore to address the gap in our knowledge of KC pathology using the proven approach of autozygosity mapping in consanguineous families segregating KC.

    The student is using autozygosity mapping to locate the mutations involved, then applying next generation sequencing technology to identify the genes. Proteins implicated are being further studied as appropriate. In addition, as an independent means to identify candidate KC genes, the student is then carrying out transcriptome analysis of keratoconic corneas to compare data with genetic findings. The new understanding obtained will facilitate informed genetic counselling, the optimisation of therapies for specific subtypes and the development of new therapeutic approaches, which will in turn reduce the morbidity and cost of this potentially blinding condition.

  • Research update

    In this project the research team discovered faults in 2 genes that are linked to keratoconus, but they are a very rare cause of the condition. The main finding was that keratoconus is much more genetically complex than we thought. It is often inherited but is caused by changes to many genes at once, none of which have a big effect on their own. The team is using the data from this project to investigate further.
  • Publications