Posterior polymorphous corneal dystrophy (PPCD) is a rare autosomal-dominant form of corneal dystrophy which affects the corneal endothelium. In severe cases, corneal endothelium failure may occur, leading to sight loss or blindness. For patients severely affected, corneal transplantation is required to restore vision.
A new genetic cause for PPCD is identified in a new study published in The American Journal of Human Genetics. The work comes from a team led by researchers from UCL Institute of Ophthalmology and Moorfields Eye Hospital London, in collaboration with colleagues in the Czech Republic.
The team pinpoints the location of a new PPCD gene and alterations in the DNA sequence that affect a gene called GRHL2. This gene is not expected to be expressed in the corneal endothelium but the team has shown that DNA changes cause the gene to be expressed inappropriately in the corneal endothelial cells. They have discovered that the endothelial cells have an ‘identity crisis’ and transition to a different state leading to dysfunction of the endothelial barrier and resulting in corneal dystrophy.
“It was a challenge to identify the DNA alterations causing PPCD because they influence how the GRHL2 gene is regulated. Most other changes in previously identified genes implicated in eye conditions affect the ‘coding’ sequence of the gene,” explains senior study author Alison Hardcastle.
“This study is not only important for understanding what is required for a healthy cornea and how it is faulty in disease, but also represents an important advance in human genetics, enhancing our understanding of the ‘non-coding’ regions of the human genome that dictate where, and when, a gene should be switched on or off.”
Fight for Sight, a leading UK-based charity focused on preventing vision loss, provided funding for the study. “We are delighted that the results from this study led to the discovery of a new genetic cause of PPCD. This will be the foundation for further studies to understand even more about the biological processes leading to corneal dystrophies and to developing new treatments,” said Neil Meemaduma, Research Manager at Fight for Sight.