New Genes to Prevent Cell Death in Glaucoma
The goal of our project is to test the neuroprotective activity of four newly identified genes in zebrafish and mammalian models of glaucoma. We will perform loss-of-function experiments in the zebrafish optic nerve crush, and bug-eye elevated intraocular pressure injury models to test if four novel zebrafish genes are neuroprotective. We expect the loss of any one of the genes will impair survival and regeneration after injury. We will then perform gain-of-function, overexpression experiments in a mammalian cell culture to test for neuroprotective effects and generate the Adeno Associated Virus (AAV) particles necessary to test each gene’s function in vivo.
Glaucoma patients and mammalian models of glaucoma-like conditions suffer vision loss due to the death of retinal ganglion cells. Under similar conditions, zebrafish retinal ganglion cells survive and regenerate damaged axons. We will use CRISPR-Cas9 gene deletion in zebrafish and gene overexpression in mammalian cells to test four novel zebrafish genes for neuroprotective activity. This basic biology research will increase our knowledge about the conditions necessary for retinal ganglion cell survival and axon regeneration under injury conditions like those seen in glaucoma. We will generate new zebrafish gene mutants and mammalian AAV vectors that will provide a resource for future study of these genes and neuroprotective pathways. We hope that the genes and pathways identified in this project will stimulate new directions in glaucoma research and one day result in new treatments to preserve or regain lost vision.