Editors' ChoiceStem Cells

Novel stem cell niche to preserve vision

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Science Translational Medicine  26 Aug 2020:
Vol. 12, Issue 558, eabd6011
DOI: 10.1126/scitranslmed.abd6011


Neural derived cells in the optic nerve express multiple stem cell markers and can differentiate into multiple neural lineages.

Glaucoma is one of the leading causes of blindness globally. It is estimated that by 2040, at least 100 million people worldwide will be afflicted by it. Irreversible blindness occurs due to optic nerve damage secondary to raised intraocular pressure in the eye. Current treatment modalities are limited to topical eye drops and ocular surgery to reduce intraocular pressure but are unable to promote optic nerve regeneration.

Bernstein et al. show that a unique population of self-replenishing, adult neural progenitor cells (NPCs) expressing Nestin and SOX2 exists in the optic nerve lamina region (ONLR) of both rodents and humans. Using green fluorescent protein (GFP)–reporter mice with SOX2-driven, inducible gene expression, they demonstrated that these NPCs were able to generate mature oligodendrocytes and astrocytes in vivo. Selective ablation of ONLR-NPCs using Cre-mediated diphtheria toxin A gene ablation resulted in loss of axonal myelination in the anterior segment of the optic nerve. Lineage tracing using ONLR cells derived from the SOX2-Cre double mutant mice confirmed that these NPCs were able to generate astrocytes, oligodendrocytes and form neurospheres in vitro. Interestingly, ONLR-NPCs became severely depleted with increasing age in both human donor and mice eyes. Together, these results suggest a physiological role of ONLR-NPCs in glial replacement and remyelination in adulthood.

This discovery potentially opens the door to new stem cell–based therapeutics for the treatment of optic neuropathies such as glaucoma. However, future research is needed to confirm the exact role of these NPCs in the development of glaucoma. In addition, the capacity of these NPCs to support optic nerve repair and regeneration has to be further explored. In particular, if researchers are able to identify and characterize the cocktail of neurotrophic growth factors secreted by these NPCs to promote optic nerve repair, it will be a useful addition to the armamentarium of therapeutic options available for the treatment of optic neuropathies such as glaucoma.

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