Genetic diseases of the optic nerve head: from embryogenesis to pathogenesis

Abstract

Retinal ganglion cells converge to leave the eye through the optic nerve head (ONH). Numerous developmental steps contribute to its complex architecture and, as a corollary, many diseases affect both ONH structure and function. Patients with cavitary disc anomalies have been found to have mutations in PAX6 and PAX2, and although PAX6 mutations have also been associated with optic nerve aplasia and hypoplasia, these specific diseases can also be caused by mutations in other genes, such as SOX2 and OTX2. The genetic mechanisms for a range of diseases causing retinal ganglion cell loss, such as glaucoma or optic atrophy, have also been investigated and although substantial insight into the molecular underpinnings for a proportion of ONH diseases has been reached, much remains to be uncovered.