Investigating corneal thinning to reduce increasing demand on corneal transplants
Researchers want to better understand what goes wrong in eye conditions where the cornea becomes extremely thin to ultimately reduce the need for corneal transplants.
Dr Veronique Vitart, who is leading a study at the University of Edinburgh, is focusing on corneal disorders such as keratoconus – the main cause of corneal transplants in the UK – as well as the very rare but devastating genetic disorder Brittle Cornea Syndrome (BCS).
BCS is characterised by extreme thinning of the cornea and most often results from rare DNA variations disrupting a poorly understood gene producing the protein ZNF469.
The role of collagen
It is suggested that the amount of functional ZNF469 protein may be very important for development of the cornea by influencing the production of type I collagen – but understanding how exactly the synthesis of this type of collagen, an essential component of a healthy cornea, is established and tuned is still poorly understood.
The corneal stroma accounts for 90% of corneal thickness in humans, and is composed of precisely organised layers of collagen fibres produced by specialised cells called keratocytes.
Abnormal stromal collagen fibres resulting in thinner cornea are seen in eye disorders such as keratoconus – which affects between one in 500 to 2,000 people worldwide - and BCS.
And while collagen cross-linking can be used to halt keratoconus progression in 90% of cases, improvement to sight remains limited (50% post treatment) -3% of patients also lose some vision as a result of haze, scarring or infection, and still require corneal transplant.
Finding alternative interventions
The team of researchers is now looking to find alternative interventions by creating a model outside the body to replicate how thinning is caused.
If successful, the model will allow for drug screening and will serve as an important research tool to find alternative interventions.
This could lead to preventing sight loss and treating patients without the need for corneal transplant.
Alternative treatment could also alleviate the pressure and demand on corneal transplants - which patients’ immune systems can react against in the case of corneal transplant rejection.
Furthermore, better understanding and characterisation of ZNF469 function may help interpreting the significance of DNA variations observed in patients presenting thin cornea.