Project details

Worldwide, about one child of every 3000 births is born with a small eye or no visible eye at all (anophthalmia or microphthalmia: AM). This is due to a developmental defect and leads to severe visual impairment, which requires surgery, counselling and long-term management to improve vision and social well being of the child. Several, but not all genes underlying AM have been identified in recent years, however how exactly they work and how their mutation leads to eye defects is unknown. This knowledge is important to develop new strategies for AM diagnosis and preventive care in the future.

The eye is composed of different tissue layers; it arises from simple cell sheets that fold and coordinate their development to form the complex structure of the adult eye. Surprisingly, the cellular processes that shape the eye are completely unknown. Basic research has identified few mechanisms that drive the formation of complex organs.

This project will determine which of these mechanisms, with a focus on the non-canonical planar cell polarity (PCP) Wnt pathway, are responsible for shaping the eye using high resolution imaging. The researchers have identified a new mouse model for AM and will use this to characterise the processes defective in AM and will test the molecular pathway that control shaping of the eye. These results will lead to a better understanding of normal and defective eye formation and our molecular analysis will uncover novel candidate genes for human AM. In the long term, collaborations with clinicians will be established to confirm that these candidates are mutated in AM individuals.