Towards a better understanding of the genetics of posterior polymorphous corneal dystrophy

Corneal Dystrophy
Research category: corneal


Aims and objectives:

Corneal diseases that affect the transparent tissue at the front of the eye can cause visual impairment.  Posterior polymorphous corneal dystrophy (PPCD) is a visually-impairing genetic disease that affects the transparent tissue at the front of the eye called the cornea. It is an abnormality of the specialised layer of cells lining the innermost surface of the tissue called the corneal endothelium. Patients with PPCD experience corneal swelling and clouding, and in some cases glaucoma, that can lead to impaired vision and/or blindness. Multiple genetic causes of PPCD have been identified, but many cases still remain genetically unsolved.

Genetic mistakes termed ‘mutations’ in genes called OVOL2 and ZEB1 are the most common known causes of PPCD, but we do not currently understand their role in the normal cornea or how they cause disease. Iridocorneal endothelial (ICE) syndrome is another disease with corneal endothelial cell dysfunction that has features similar to PPCD but, unlike PPCD, patients typically present with unilateral disease and no family history of the condition. However, the aetiology (causation of disease) of ICE syndrome is currently unknown. Corneal transplantation is currently the only treatment option available for advanced stage PPCD and ICE syndrome but the long term survival of grafts is poor. Surgery also relies upon specialist facilities and healthy donor material, of which there is a currently a global shortage.

Work being carried out:

Tissue samples from patients with PPCD or ICE recruited at Moorfields Eye Hospital will be analysed to establish the potential genetic causes of disease.  The tissue samples will also be used to grow corneal tissue in the laboratory which can then be used to investigate how the diseases progress. As part of the project, the research team will also use tissue removed during corneal transplant surgery to investigate potential viral causes of ICE syndrome and the genetic code of PPCD to elucidate the pathogenic mechanisms associated with different causes of disease.

Outcomes and impact:

It is anticipated that this PhD Studentship will result in the identification of new genetic cause(s) of PPCD. This knowledge will facilitate appropriate genetic counselling and will inform the clinical management of patients. The team will also to establish whether ICE syndrome can be attributed to genetic and /or viral causes. In addition, by studying the biological basis of PPCD and ICE syndrome, using patient-derived cells, and will lead to the identification of common biomarkers of disease, that in the longer-term, will act as therapeutic targets for the develop non-surgical treatments for these conditions.

Research details

Full Title

Investigating genetic causes and transcriptional dysregulation events associated with posterior polymorphous corneal dystrophy (PPCD)

Grant holder

Dr Alice Davidson

Research Area(s)


Start date

May 2018


Date: 23 August 2018

Grant reference: R180021A