Subtype-Specific Regeneration of Retinal Ganglion Cells following Axotomy: Effects of Osteopontin and mTOR Signaling

摘要

In mammals, fewretinal 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 (aRGCs) surviving preferentially. Among survivors, aRGCs accounted for nearly all regeneration following downregulation of PTEN, which activates the mTOR pathway. aRGCs 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 aRGCs. 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.