Protective effects of selegiline and desmethylselegiline against N-methyl-D-aspartate-induced rat retinal damage.
Selegiline, a therapeutic agent of Parkinson's disease, and its metabolite, desmethylselegiline, were explored for their neuroprotective effects against N-methyl-D-aspartate (NMDA)-induced cell death in rat retina. Morphometric analysis of the retina revealed that an intravitreal injection of NMDA induced a significant decrease in cell density in the ganglion cell layer and in thickness of the inner plexiform layer, but not of other retinal layers such as the outer nuclear layer. Concurrent intravitreal injection of selegiline with NMDA did not show a significant protective effect, whereas co-injection of desmethylselegiline provided protection from NMDA-induced retinal damage. Parenteral administration (both single and consecutive dosing) of selegiline significantly prevented loss of ganglion cell layer cells. Counting of retinal ganglion cells by fluorescent tracer labeling confirmed that selegiline protected retinal ganglion cells from NMDA toxicity. The selegiline treatment did not produce a significant increase, though it tended to such as effect, in a brain-derived neurotrophic factor (BDNF) level in the retina, when compared with the NMDA-treated control group. These results indicate that parenteral treatment with selegiline rescues inner retinal cells from NMDA-induced neural damage, and that desmethylselegiline may contribute, in part, to the protective activities of selegiline. The neuroprotective effects exerted by selegiline may be attributed partially to a change in the retinal BDNF expression.
Takahata
Kazue
K
Institute of Research and Development, Fujimoto Pharmaceutical Corporation, 1-3-40 Nishiotsuka, Osaka 580-8503, Matsubara, Japan.
Katsuki
Hiroshi
H
Kobayashi
Yutaka
Y
Muraoka
Shizuko
S
Yoneda
Fumio
F
Kume
Toshiaki
T
Kashii
Satoshi
S
Honda
Yoshihito
Y
Akaike
Akinori
A
D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000494:pharmacology; D007267:Injections; D007279:Injections, Subcutaneous; D008297:Male; D016202:N-Methylaspartate / Q000008:administration & dosage; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D012642:Selegiline / Q000494:pharmacology*; D013477:Superior Colliculi / Q000187:drug effects / Q000378:metabolism; D014822:Vitreous Body
D000662:Amphetamines; D019208:Brain-Derived Neurotrophic Factor; D018696:Neuroprotective Agents; D012642:Selegiline; C017861:desmethylselegiline; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate