Epigenomic Analysis of Sorted Retinal Ganglion Cells using ATAC-seq

Glaucoma is a group of diseases with diverse molecular mechanisms of pathogenesis, all of which converge on a common pathway leading to typical optic nerve damage, loss of retinal ganglion cells and, consequently, loss of vision. Retinal ganglion cells (RGCs) are the brain’s only visual connection to the outside world and, despite numerous studies, there is not yet successful therapy to prevent their loss in glaucoma. Several studies have identified nonsynonymous coding variant SIX6-rs33912345 His141Asn as strongly associated with glaucoma. To directly assess the functional relevance of Six6-141His versus Six6-141Asn variants in eye function, transcriptomic and epigenetic changes in RGC isolated from mouse strains expressing the “protective” and “risk” SIX6 allele were assessed. A murine model of glaucoma was established by raising intraocular pressure (IOP), which serves as the mechanism of RGC injury.