Testing Lens-Derived Signaling Pathways in Ocular Dysgenesis

Douglas Gould, PhD University of California, San Francisco


Normal eye development is a complex process that is poorly understood. People with small developmental defects in the front of the eye are at very high risk of going blind as children or young adults. We are studying genes involved in normal eye development so that we may understand how defects lead to blindness from glaucoma and other diseases, and if there are ways to intervene and prevent vision loss.

Project Details

The goal of this project is to understand how cells communicate with each other during development in order to form a functional eye.

During development, cells from multiple different origins must work together in a coordinated fashion. In order to coordinate their movements and adopt specialized functions, the cells must communicate with each other. When the molecular signals that they use to communicate are disrupted, the messages are not delivered, and developmental abnormalities occur. In the case of the ocular anterior segment, these developmental abnormalities can lead to elevated intraocular pressure and early-onset glaucoma.

For the first part of our proposal, we are working to identify signals that are sent from the lens to the surrounding tissues that instruct them on how to develop into functional structures of the anterior segment of the eye.

The second part of our proposal concerns the cells that receive the signal – the neural crest cells. Neural crest cells are a special population of multi-functional cells that arose in vertebrates. These cells require context-dependent cues in order to make up most of the structures in the front of the eye. We are studying how these cells integrate molecular messages and how they behave when the messages are not delivered properly. 

The importance of intercellular communication and neural crest cell differentiation have been known for many years. However, the neural crest cell population in the developing eye is very small and that makes it challenging to study. Recent technological advances allow for molecular profiling of small populations of inaccessible cells, and we will use these techniques to compare the molecular signatures of neural crest cells in the developing eye in normal and diseased states.

At the conclusion of our study, we will have a more complete understanding of the molecular events that occur during normal ocular development and what goes wrong in the case of an ocular disease. Understanding how and when developmental abnormalities occur could lead to the identification of potential therapeutic targets for developmental glaucoma.