Funding outcome

Globally, 217 million people live with severe visual impairment, with 36 million people blind (World Health Organization). Our studies focus on children with blinding disorders that are present at birth. Our reseach concerns a disease known as coloboma, in which a gap is present in tissues of the eye. This is frequently observed as a keyhole pupil in which the normally round pupil is elongated, thereby resembling the eye of a cat. Coloboma is the second leading cause of pediatric blindness, representing 11-15% of blind children. Yet we lack an understanding of the mechanisms by which this disorder occurs. We have been studying two types of coloboma in children, with cases affecting the lower or upper portions of the eye. or each we have recently identified good candidate changes in the DNA of affected individuals. These changes lie in individual 'genes' yet we cannot be sure that they cause disease or represent alterations due to random chance. Therefore, the next and most critical step in the research is to test the hypothesis that such detected changes are indeed the cause of the patient's disease. To accomplish this, we switch our research from human patients to studies of animal models. Our research uses a small tropical fish as a method for studying blinding disorders. The first step of such research is the creation of an animal model in which the candidate disease causing gene is eliminated. We then grow the fish embryos, allowing the eye to develop and determine whether the eye is misshapen, resembling human patients with coloboma. If we observe such alterations to ocular development in the animal model, this strongly supports the model that this candidate is likely a disease-causing gene. The next step of the research is to quantiatively measure the activity of the detected disease causing candidate. We develop assays, again in animal models, whereby we can assess the activity of our factors. We then compare the activity of these factors isolated from either normal or blind patients. If we observe a large loss of activity in the patient factor, this tells us that this is likely a disease-causing gene. Once our research is complete, we communicate our results to doctors and counselors, and they work together with children and families to increase the understanding of their disease.