beta-N-methylamino-L-alanine induced in vivo retinal cell death.

Controversial debates still remain around the nature of the etiologic agent responsible for Amyotrophic lateral sclerosis/Parkinson dementia complex (ALS/PDC) whose incidence is unusually high among the population of the pacific island of Guam. It has been hypothesized that the neurotoxin beta-N-methylamino-L-alanine (L-BMAA) produced by cyanobacteria in the roots of Cycas Circinalis seeds might trigger ALS/PDC. Frequently observed in patients with ALS/PDC, retinopathy is one of the clinical features of the disease. The effect of the L-BMAA on cell viability was examined in vivo by measuring the electrophysiological activity of the mouse retinal neurons by electroretinography recordings. Intra-ocular injections of L-BMAA selectively reduced the b-wave amplitude, without affecting neither the a-wave amplitude nor the a- and b-latencies. The cell death of retinal cells was evidenced by histology on retina sections, caspase 3 activation, incorporation of propidium iodide and production of reactive oxygen species. Co-injection with the specific NMDA antagonist, MK-801, significantly protected the retinal neurons from L-BMAA/NMDA-induced apoptosis. We provide evidence that L-BMAA induced neuronal cell death in vivo supporting a direct causal link between L-BMAA and neuronal damages.