The optic nerve lamina region is a neural progenitor cell niche

Abstract

Retinal ganglion cell axons forming the optic nerve (ON) emerge unmyelinated from the eye and become myelinated after passage through the optic nerve lamina region (ONLR), a transitional area containing a vascular plexus. The ONLR has a number of unusual characteristics: it inhibits intraocular myelination, enables postnatal ON myelination of growing axons, modulates the fluid pressure differences between eye and brain, and is the primary lesion site in the age-related disease open angle glaucoma (OAG). We demonstrate that the human and rodent ONLR possesses a mitotically active, age-depletable neural progenitor cell (NPC) niche, with unique characteristics and culture requirements. These NPCs generate both forms of macroglia: astrocytes and oligodendrocytes, and can form neurospheres in culture. Using reporter mice with SOX2-driven, inducible gene expression, we show that ONLR-NPCs generate macroglial cells for the anterior ON. Early ONLR-NPC loss results in regional dysfunction and hypomyelination. In adulthood, ONLR-NPCs may enable glial replacement and remyelination. ONLR-NPC depletion may help explain why ON diseases such as OAG progress in severity during aging.