McMahon, Carrie

My project centers on the ocular function of two specific zebrafish genes known to be mutated in human glaucoma: lmx1b and myocilin. Lmx1b is a LIM homeodomain transcription factor and loss-of-function mutations in lmx1b have been shown to cause juvenile-onset open angle glaucoma. To test the role of lmx1b mutations, I plan to design morpholinos to knock-down lmx1b function in zebrafish embryos. Embryos without lmx1b will be assessed for gross abnormalities and development of the ocular anterior segment. Myocilin is a large glycoprotein with unknown function. Gain-of-function mutations in this gene also results in juvenile-onset open angle glaucoma. Because glaucoma-causing mutations in myocilin are thought to be gain-of-function, I will investigate the consequences of over-expressing the disease form of myocilin in transgenic zebrafish. Adult transgenic fish will then be assessed for glaucoma phenotypes such as elevated intraocular pressure and retinal ganglion cell loss.