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.