Protective Effects of Selegiline Against Glutamate Neurotoxicity in Cultured Retinal Neurons

Abstract

Abstract: : Purpose: To study the effect of selegiline, a selective monoamine oxidase–B inhibitor, and its metabolite, desmethylselegiline, on glutamate neurotoxicity in cultured retinal neurons. Methods: Primary cultures were obtained from fetal rat retinae (gestation day 17–19). Cytosine arabinoside (10 µM) was added to the culture on the 6th day to eliminate non–neuronal cells. We used only those cultures maintained for 7–8 days in vitro. Glutamate neurotoxicity was assessed by 10–min exposure to 1mM glutamate followed by 1–hour incubation in glutamate–free media, using the trypan blue exclusion method. Selegiline or desmethylselegiline were applied simultaneously with 1mM glutamate. Results: Ten–min exposure to glutamate followed by 1–hour incubation reduced cell viability by 20–40%. Simultaneous application of selegiline (1, 10, 100 µM) and glutamate (1mM) inhibited retinal neuronal cell death induced by glutamate in a dose–dependent manner. Cell viability was also restored by co–application of 10 µM desmethylselegiline, a selegiline metabolite, with glutamate (1mM) in a similar manner to that seen with selegiline (10 µM). Conclusions: These results suggest that selegiline or its desmethyl metabolite has a protective action against glutamate–induced neurotoxicity in cultured retinal neurons.

Keywords: excitatory amino acid receptors • retinal culture • cell death/apoptosis