Unravelling the molecular complexity behind ocular maldevelopment

Eye birth defects, known as ocular maldevelopment, including abnormally small eyes, clefts of the eye and complete absence of any eyes, occur within the first 4-9 weeks of pregnancy. They cause over a third of the cases of blindness in children worldwide, resulting in profound life-long problems for both the patient and their family. Only a few genes have been found to cause ocular maldevelopment, the majority remain undiscovered and currently there is no treatment available.

The goals of this study are to determine the genetic causes of ocular maldevelopment while carefully detailing the disease characteristics over time to see if any specialist care is needed to minimise associated health problems. Another aim is to identify chemical changes, called methylation, in our DNA that influence genes being switched on or off at crucial points during normal eye development, to form a reference guide for comparison with patients. Using this information, a 3D model of the developing eye will be made from stem cells derived from patient’s skin to investigate changes in genes that cause ocular maldevelopment. This will allow us to develop new therapies.

Once we understand the genetic causes, a real focus on treatments can be made. This study will allow accurate diagnosis and genetic counselling and improved care pathways for patients and families.