Investigating genetics underlying inherited corneal disease

Brief Lay Background

The cornea is the transparent window of tissue situated at the front of the eye. It protects the eye from the external environment and its curved symmetrical shape allows it to focus light onto the retina.

However, due to ‘spelling mistakes’ in the genetic code (mutations), some individuals suffer from Inherited Corneal Disease (ICD) which causes their corneal tissue to lose its transparency and/or shape, leading to severe loss of vision or even blindness.

What problem/knowledge gap does it help address

At the moment, corneal transplantation surgery is the only treatment option available for the vast majority of ICD patients. However, the long-term survival of corneal grafts can be poor if the disease returns in the transplanted tissue, which means that some patients require multiple transplants during their lifetime. Surgery also relies upon specialist facilities and healthy donor corneas, of which there are currently a global shortage.

There is therefore an urgent need to develop alternative treatment approaches which target the specific genetic cause of the disease. This would reduce the reliance on donor tissues and provide less-invasive therapeutic options that would be tailored to individual patient needs. This has been identified as a research priority by patient engagement groups.

Aim of the research project

To identify the underlying genetic mutations that cause ICDs and to study how these mutations alter the normal functioning of the corneal tissue. Understanding this is the first step towards developing new therapeutic strategies that can target these mutations directly and/or their downstream effects.

Key procedures/Objectives

1. Discover novel genetic cause(s) responsible for unsolved ICD
2. Leverage publicly available corneal data to better understand why cellular and genetic changes cause ICD
3. Improve ways of diagnosing and managing ICD through enhanced knowledge of underlying genetic causes and molecular mechanisms

Impact on people with sight loss

Developing ways to help solve unexplained ICDs will enable the student to identify the novel genetic causes that are responsible. For patients affected by ICDs, a genetic diagnosis helps clinicians develop an effective care plan whilst giving the patient an understanding of their condition, both for themselves and for their family.

ICD-related genetics remains an understudied and underfunded area of research. This situation, in combination with a global shortage of appropriate donor tissue for corneal transplant surgeries, means that new innovative therapies that are not reliant on donor tissues are urgently required to improve patient care for this visually disabling group of conditions.