Combinatorial therapy stimulates long-distance regeneration, target reinnervation, and partial recovery of vision after optic nerve injury in mice

Int Rev Neurobiol. 2012;106:153-72. doi: 10.1016/B978-0-12-407178-0.00007-7.

Abstract

The optic nerve has been widely studied for insights into mechanisms that suppress or promote axon regeneration after central nervous system injury. Following optic nerve damage in adult mammals, retinal ganglion cells (RGCs) normally fail to regenerate their axons, resulting in blindness in patients who suffer from neurodegenerative diseases such as glaucoma or who have sustained traumatic injury to the optic nerve. Over the past several decades, many groups have investigated the basis of regenerative failure in the hope of developing strategies to stimulate the regrowth of axons and restore visual function. New findings show that a combination of therapies that act synergistically to activate RGCs' intrinsic growth state enables these cells to regenerate their axons the full length of the optic nerve, across the optic chiasm, and into the brain, where they establish synapses in appropriate target zones and restore limited visual responses. These treatments involve the induction of a limited inflammatory response in the eye to increase levels of oncomodulin and other growth factors; elevation of intracellular cAMP; and deletion of the pten gene in RGCs. Although these methods cannot be applied in the clinic, they point to strategies that might be.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Genetic Therapy / methods
  • Humans
  • Mice
  • Nerve Growth Factors / pharmacology
  • Nerve Growth Factors / therapeutic use
  • Nerve Regeneration / drug effects
  • Nerve Regeneration / physiology*
  • Optic Nerve Injuries / genetics
  • Optic Nerve Injuries / physiopathology
  • Optic Nerve Injuries / therapy*
  • Recovery of Function / physiology*
  • Retinal Ganglion Cells / drug effects
  • Retinal Ganglion Cells / physiology
  • Vision, Ocular / drug effects
  • Vision, Ocular / physiology*

Substances

  • Nerve Growth Factors