Project 458198

While the eye is developing, a temporary opening forms below the eye that guides blood vessels and nerves into the eye. If this opening doesn't close properly, it can cause a pinhole-like defect and a condition called coloboma. Coloboma is a significant cause of blindness in children and is responsible for 10% of pediatric blindness. Our lab has been the first to report a similar but distinct condition called superior coloboma in patients with a pinhole-like defect above their eyes. We have shown the existence of an opening above the eye, in addition to the opening below, which if not closed properly can cause superior coloboma. However, the genetic causes of superior coloboma are still unknown. Our preliminary results have shown that genetic pathways in cell polarity might be involved in the closure of the opening above the eye. My project will aim to investigate the genes and proteins responsible for the formation and closure of the opening above the eye by studying the role of these genetic pathways using zebrafish as a model for human disease. I will generate mutations in the zebrafish genes of the cell polarity pathways we have implicated in the closure of the opening above the eye. The patterns and associations of gene and protein expression will then be investigated in these mutant zebrafish using novel multi-omics techniques. I will analyze the results using innovative artificial intelligence algorithms and use molecular biology techniques to confirm those results. My work will increase our understanding of how and what genes and proteins work together to guide early development and how they are changed in developmental disorders. This work can also lower the burden of disease by using newer technologies to prevent, diagnose, and treat eye diseases, especially coloboma.