Damaging effects of BMAA on retina neurons and Müller glial cells

• Published in: Experimental eye research Vol. 202; p. 108342
• Main Authors: Soto, Tamara, Buzzi, Edgardo D., Rotstein, Nora P., German, O. Lorena, Politi, Luis E.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.01.2021
• Subjects: Amacrine neurons; Amino Acids, Diamino - toxicity; Animals; Animals, Newborn; B-N-Methylamino-L-alanine toxicity; Cell Survival - drug effects; Dizocilpine Maleate - pharmacology; DNA Fragmentation - drug effects; Ependymoglial Cells - drug effects; Ependymoglial Cells - pathology; Excitatory Amino Acid Agonists - toxicity; Excitatory Amino Acid Antagonists - pharmacology; Membrane Potential, Mitochondrial - drug effects; Müller glial cells; PC12 cells; Photoreceptors; Rats; Rats, Wistar; Reactive Oxygen Species - metabolism; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors; Retinal Diseases - chemically induced; Retinal Diseases - metabolism; Retinal Diseases - prevention & control; Retinal Neurons - drug effects; Retinal Neurons - pathology; Amacrine neurons; Photoreceptors; PC12 cells; Müller glial cells; B-N-Methylamino-L-alanine toxicity
• ISSN: 0014-4835; 1096-0007
• DOI: 10.1016/j.exer.2020.108342

B–N-methylamino-L-alanine (BMAA), a cyanotoxin produced by most cyanobacteria, has been proposed to cause long term damages leading to neurodegenerative diseases, including Amyotrophic Lateral Sclerosis/Parkinsonism Dementia complex (ALS/PDC) and retinal pathologies. Previous work has shown diverse mechanisms leading to BMAA-induced degeneration; however, the underlying mechanisms of toxicity affecting retina cells are not fully elucidated. We here show that BMAA treatment of rat retina neurons in vitro induced nuclear fragmentation and cell death in both photoreceptors (PHRs) and amacrine neurons, provoking mitochondrial membrane depolarization. Pretreatment with the N-Methyl-D-aspartate (NMDA) receptor antagonist MK-801 prevented BMAA-induced death of amacrine neurons, but not that of PHRs, implying activation of NMDA receptors participated only in amacrine cell death. Noteworthy, BMAA stimulated a selective axonal outgrowth in amacrine neurons, simultaneously promoting growth cone destabilization. BMAA partially decreased the viability of Müller glial cells (MGC), the main glial cell type in the retina, induced marked alterations in their actin cytoskeleton and impaired their capacity to protect retinal neurons. BMAA also induced cell death and promoted axonal outgrowth in differentiated rat pheochromocytoma (PC12) cells, implying these effects were not limited to amacrine neurons. These results suggest that BMAA is toxic for retina neurons and MGC and point to the involvement of NMDA receptors in amacrine cell death, providing new insight into the mechanisms involved in BMAA neurotoxic effects in the retina. •BMAA damages retinal neurons and Muller glial cells and promotes axonal outgrowth in amacrine cells.•BMAA damages retinal neurons and Muller glial cells.•BMAA promotes axonal outgrowth in amacrine cells.