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.

The Potential of Visible and Far-Red to Near-Infrared Light in Glaucoma Neuroprotection

“…These findings are of relevance, as Bernstein et al recently demonstrated that the optic nerve lamina region (ONLR) contains a neural progenitor cell (NPC) niche, which may have a role in both postnatal optic nerve development and in adult optic nerve support and repair [56]. Unmyelinated retinal ganglion cell axons originating in the retina pass through the ONLR, the most anterior portion of the optic nerve, before myelination occurs in the more distal portion of the optic nerve.…”

“…Unmyelinated retinal ganglion cell axons originating in the retina pass through the ONLR, the most anterior portion of the optic nerve, before myelination occurs in the more distal portion of the optic nerve. However, the precise sites of postnatal RGC axonal growth and the mechanism by which myelination occurs at sites of newly formed axonal membrane late in postnatal growth are still obscure [56]. It is well known that ONLR has a number of unusual characteristics: it inhibits intraocular myelination, enables postnatal optic nerve myelination of growing axons, modulates the fluid pressure differences between eye and brain, and is the primary lesion site in age-related open-angle glaucoma.…”

Diversity of Adult Neural Stem and Progenitor Cells in Physiology and Disease

“…Cells from regions of the adult retina such as the retinal pigment epithelium (RPE) [47,48], CE [49][50][51][52][53], Müller glia cells [51,[54][55][56], iris pigment epithelium [57,58] and optic nerve [48] show stem cell characteristics to varying degrees (Figure 2C). Among them, the CE and Müller glia are identified as two main retinal stem cell sources.…”

“…A subpopulation of adult human RPE cells is capable of being activated to become RPE retinal stem cells in vitro and differentiated into multipotent stable RPE or mesenchymal lineages [47]. The optic nerve lamina region (ONLR) in both humans and mice contains a retinal NPC niche [48]. Adult NPCs in the ONLR exhibit multipotency and generate two types of glia: astrocytes and oligodendrocytes.…”

“…Adult NPCs in the ONLR exhibit multipotency and generate two types of glia: astrocytes and oligodendrocytes. These populations contribute to enable glial replacement and remyelination in adulthood [48]. The derived adult rat iris pigment epithelium (IPE) cells have NSPC differentiation ability to differentiate into rod photoreceptor cells under CRX transfer [58].…”