Neuron
Volume 85, Issue 6, 18 March 2015, Pages 1244-1256
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Article
Subtype-Specific Regeneration of Retinal Ganglion Cells following Axotomy: Effects of Osteopontin and mTOR Signaling

https://doi.org/10.1016/j.neuron.2015.02.017Get rights and content
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Highlights

  • RGC subtypes differ dramatically in ability to survive axotomy

  • Αxotomized αRGCs regenerate preferentially when mTOR signaling is stimulated

  • αRGCs selectively express osteopontin and IGF1 receptors

  • Administration of osteopontin plus IGF1 promotes αRGC axon regeneration

Summary

In mammals, few retinal ganglion cells (RGCs) survive following axotomy, and even fewer regenerate axons. This could reflect differential extrinsic influences or the existence of subpopulations that vary in their responses to injury. We tested these alternatives by comparing responses of molecularly distinct subsets of mouse RGCs to axotomy. Survival rates varied dramatically among subtypes, with alpha-RGCs (αRGCs) surviving preferentially. Among survivors, αRGCs accounted for nearly all regeneration following downregulation of PTEN, which activates the mTOR pathway. αRGCs have uniquely high mTOR signaling levels among RGCs and also selectively express osteopontin (OPN) and receptors for the insulin-like growth factor 1 (IGF-1). Administration of OPN plus IGF-1 promotes regeneration as effectively as downregulation of PTEN; however, regeneration is still confined to αRGCs. Our results reveal dramatic subtype-specific differences in the ability of RGCs to survive and regenerate following injury, and they identify promising agents for promoting axonal regeneration.

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Present address: Department of Ophthalmology, Yale University School of Medicine, New Haven, CT 06510, USA