Optic nerve and neuroprotection strategies

Eye (Lond). 2004 Nov;18(11):1075-84. doi: 10.1038/sj.eye.6701588.

Abstract

Background: Experimental studies have yielded a wealth of information related to the mechanism of ganglion cell death following injury either to the myelinated ganglion cell axon or to the ganglion cell body. However, no suitable animal models exist where injury can be directed to the optic nerve head region, particularly the unmyelinated ganglion cell axons. The process of relating the data from the various animal models to many different types of optic neuropathies in man must, therefore, be cautious.

Results: Extensive studies on the isolated optic nerve have yielded valuable information on the way white matter is affected by ischaemia and how certain types of compounds can attenuate the process. Moreover, there are now persuasive data on how ganglion cell survival is affected when the ocular blood flow is reduced in various animal models. As a consequence, the molecular mechanisms involved in ganglion cell death are fairly well understood and various pharmacological agents have been shown to blunt the process when delivered before or shortly after the insult.

Conclusions: A battery of agents now exist that can blunt animal ganglion cell death irrespective of whether the insult was to the ganglion cell body or the myelinated axon. Whether this information can be applied for use in patients remains a matter of debate, and major obstacles need to be overcome before the laboratory studies may be applied clinically. These include the delivery of the pharmacological agents to the site of ganglion cell injury and side effects to the patients. Moreover, it is necessary to establish whether effective neuroprotection is only possible when the drug is administered at a defined time after injury to the ganglion cells. This information is essential in order to pursue the idea that a neuroprotective strategy can be applied to a disease like glaucoma, where ganglion cell death appears to occur at different times during the lifetime of the patient.

Publication types

  • Review

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / physiology
  • Axons / physiology
  • Disease Models, Animal
  • Glaucoma / drug therapy
  • Glaucoma / physiopathology
  • Humans
  • Neuroprotective Agents / therapeutic use*
  • Optic Disk / drug effects
  • Optic Disk / physiopathology
  • Optic Nerve / drug effects*
  • Optic Nerve / physiopathology
  • Optic Nerve Diseases / drug therapy*
  • Optic Nerve Diseases / physiopathology
  • Optic Nerve Injuries / drug therapy
  • Optic Nerve Injuries / physiopathology
  • Optic Neuropathy, Ischemic / drug therapy
  • Optic Neuropathy, Ischemic / physiopathology
  • Rats
  • Retinal Ganglion Cells / drug effects*
  • Retinal Ganglion Cells / physiology

Substances

  • Neuroprotective Agents