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The basic science of optic nerve regeneration.

ABSTRACT: Diverse insults to the optic nerve result in partial to total vision loss as the axons of retinal ganglion cells are destroyed. In glaucoma, axons are injured at the optic nerve head; in other optic neuropathies, axons can be damaged along the entire visual pathway. In all cases, as mammals cannot regenerate injured central nervous system cells, once the axons are lost, vision loss is irreversible. However, much has been learned about how retinal ganglion cells respond to axon injuries, and many of these crucial discoveries offer hope for future regenerative therapies. Here we review the current understanding regarding the temporal progression of axonal degeneration. We summarize known survival and regenerative mechanisms in mammals, including specific signaling pathways, key transcription factors, and reprogramming genes. We cover mechanisms intrinsic to retinal ganglion cells as well as their interactions with myeloid and glial cell populations in the retina and optic nerve that affect survival and regeneration. Finally, we highlight some non-mammalian species that are able to regenerate their retinal ganglion cell axons after injury, as understanding these successful regenerative responses may be essential to the rational design of future clinical interventions to regrow the optic nerve. In the end, a combination of many different molecular and cellular interventions will likely be the only way to achieve functional recovery of vision and restore quality of life to millions of patients around the world.

SUBMITTER: Fague L

PROVIDER: S-EPMC8421956 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Oncomodulin links inflammation to optic nerve regeneration.

Project description:The inflammatory response that accompanies central nervous system (CNS) injury can affect neurological outcome in both positive and negative ways. In the optic nerve, a CNS pathway that normally fails to regenerate when damaged, intraocular inflammation causes retinal ganglion cells (RGCs) to switch into an active growth state and extend lengthy axons down the nerve. The molecular basis of this phenomenon is uncertain. A prior study showed that oncomodulin (Ocm), a Ca(2+)-binding protein secreted by a macrophage cell line, is a potent axon-promoting factor for RGCs. However, it is not known whether Ocm contributes to the physiological effects of intraocular inflammation in vivo, and there are conflicting reports in the literature regarding its expression and significance. We show here that intraocular inflammation causes infiltrative cells of the innate immune system to secrete high levels of Ocm, and that agents that prevent Ocm from binding to its receptor suppress axon regeneration. These results were verified in different strains, species, and experimental models, and establish Ocm as a potent growth-promoting signal between the innate immune system and neurons in vivo.

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