[Neuroprotection and regeneration after traumatic lesion of the optic nerve].
BACKGROUND
After a traumatic lesion of the optic nerve, retinal ganglion cells (RGC) undergo massive degeneration by apoptosis, which leads to loss of vision in the affected eye. Like other neurones in the central nervous system, RGC are not able to regenerate their damaged axons spontaneously. We used special surgical methods and pharmacological measures to achieve enhanced survival and regeneration of damaged RGC.


METHODS
Studies were performed using the model of RGC degeneration induced by severing the optic nerve of adult rats. RGC were loaded with a fluorescent dye, and several drugs were applied intravitreally. The effects were evaluated after two weeks by counting the surviving RGC. For regeneration studies, an autologous peripheral nerve graft was sutured to the stump of the cut optic nerve, or the ends of the cut optic nerve were re-sutured. Recovery of RGC function was assessed by VEP measurements.


RESULTS
The number of RGC surviving an axotomy increased significantly after intravitreal injections of aurintricarboxylic acid, cortisol, a caspase inhibitor, brimonidine or microglia-targeted substances. Regeneration of cut axons was enhanced by aurintricarboxylic acid or cortisol. In addition, considerable neuroprotective and regenerative effects including partial restoration of VEP were induced by lens injury, which results in a gradual release of crystallins into the vitreous, or by intravitreal injection of purified crystallins.


CONCLUSIONS
The loss of vision after an optic nerve trauma can be reduced in this animal model by suitable neuroprotective measures, which raises hope for the treatment of patients.
Heiduschka
P
P
Novartis Pharma AG, NIBR, WKL-126.3.05, Klybeckstr., Porte 15, CH-4002 Basel, Schweiz. peter.heiduschka@pharma.novartis.com
Fischer
D
D
Thanos
S
S
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology*; D016501:Neurites / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D019635:Neurosurgical Procedures / Q000379:methods; D013508:Ophthalmologic Surgical Procedures / Q000379:methods*; D020221:Optic Nerve Injuries / Q000473:pathology* / Q000628:therapy*; D051381:Rats; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000473:pathology*; D016896:Treatment Outcome
D018696:Neuroprotective Agents