USING AN ANIMAL MODEL TO UNDERSTAND COLOBOMA-ELUCIDATION OF THE GENETIC MECHANISMS UNDERLYING CHOROID FISSURE CLOSURE.

The eye is a complex organ composed of many different parts (such us the cornea, iris, lens, vitreous body, retina and optic nerve) each vital for a correct vision. Hereditary ocular diseases, due to abnormal developmental processes, are common in the human population, since they are often compatible with life and reproduction. Among these, coloboma (a Greek word which means "mutilation") is an eye defect in which there is an open fissure within the eye, caused by non closure of the optic fissure during embryonic morphogenesis of the eye. The open fissure can affect different eye structures including the retina, iris, choroid and optic nerve. Not surprisingly this can cause from mild to severe deficiencies in vision, such as retinal detachment, myopia, reduction of visual acuity, defective visual fields, strabismus and subnormal electroretinographies. In humans, frequency estimates for isolated coloboma range from about 5 to 26 per 100,000 and the available data suggest that many genes are probably involved. Despite its developmental and clinical importance, optic fissure closure is still a poorly understood phenomenon. In this proposed project, I will use an experimentally tractable model system, the zebrafish, as an experimental system to identify and functionally characterise genes potentially involved in human hereditary forms of coloboma. The strength of this proposal comes from the extreme conservation of genes and molecular mechanisms responsible for vertebrate eye development. There are several clear examples of how basic studies on eye development in simple vertebrates have led to the identification of the genes responsible for ocular diseases in human. Basic knowledge on optic vesicle closure will provide in the future not only the basis to understand the nature of inheritable eye diseases, coloboma and similar, but also the necessary means for the prevention, diagnosis and treatment.