Neuroprotection for optic nerve disorders.
OBJECTIVE
The concept that optic nerve fiber loss might be reduced by neuroprotection arose in the mid 1990s. The subsequent research effort, focused mainly on rodent models, has not yet transformed into a successful clinical trial, but provides mechanistic understanding of retinal ganglion cell death and points to potential therapeutic strategies. This review highlights advances made over the last year.


RESULTS
In excitotoxicity and axotomy models retinal ganglion cell death has been shown to result from a complex interaction between retinal neurons and Müller glia, which release toxic molecules including tumor necrosis factor alpha. This counteracts neuroprotection by neurotrophins such as nerve growth factor, which bind to p75NTR receptors on Müller glia stimulating the toxic release. Another negative effect against neurotrophin-mediated protection involves the action of LINGO-1 at trkB brain-derived neurotrophic factor (BDNF) receptors, and BDNF neuroprotection is enhanced by an antagonist to LINGO-1. As an alternative to pharmacotherapy, retinal defences can be stimulated by exposure to infrared radiation.


CONCLUSIONS
The mechanisms involved in glaucoma and other optic nerve disorders are being clarified in rodent models, focusing on retrograde degeneration following axonal damage, excitotoxicity and inflammatory/autoimmune mechanisms. Neuroprotective strategies are being refined in the light of the mechanistic understanding.
Bessero
Anne-Caroline
AC
Department of Neuro-Ophthalmology, The National Hospital for Neurology and Neurosurgery, London, UK. anncaroline.bessero@uclh.nhs.uk
Clarke
Peter G H
PG
D000975:Antioxidants / Q000627:therapeutic use*; D005901:Glaucoma / Q000473:pathology / Q000517:prevention & control / Q000628:therapy; D006801:Humans; D007259:Infrared Rays / Q000627:therapeutic use*; D007429:Intraocular Pressure; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D009901:Optic Nerve Diseases / Q000517:prevention & control* / Q000628:therapy*; D012165:Retinal Ganglion Cells / Q000473:pathology; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000627:therapeutic use
D000975:Antioxidants; D014451:Ubiquinone; D019001:Nitric Oxide Synthase; C024989:coenzyme Q10