Neurodegenerative effects of the cyanotoxin β-n-methylamino-l-alanine (BMAA) on retinal cells

SOTO, TAMARA; TENCONI, PAULA E.; MATEOS, MELINA V.; POLITI, LUIS ENRIQUE; GERMAN, OLGA L.

Mar del Plata

Congreso; REUNIÓN CONJUNTA SAIC - SAI & FAIC - SAFIS 2022; 2022

The chronic intake of the non-proteic aminoacid BMAA, a cyanotoxin released by many cyanobacteria occurring in most dams and water resources, was linked with the development of neurodegenerative diseases. We previously, demonstrated that BMAA generates cell death in amacrine and photoreceptor neurons (PHRs) and that NMDA receptors induce amacrine cell death through β-carbamate production. We here investigated whether BMAA is mis-incorporated into polypeptide chains of retinal neurons, replacing serine, thus triggering neurodegenerative processes. Also, we investigated the neuroprotective role of RXRs receptors, and the effects of BMAA on a retinal pigment epithelial cell line (ARPE-19). We incubated pure neuronal cultures obtained from newborn rat retinas with 0,4 µM BMAA, and ARPE-19 cells with 0,4, 1 and 10 µM of BMAA during 3 days. We then evaluated cell death and apoptosis by Trypan Blue, TUNEL assays, and DAPI staining; mitochondrial activity by Mitotracker and MTT assays; ROS levels by using the probe H2-DCFDA and cytoskeleton integrity by immunocytochemical methods. In pure neuronal cultures, pre-treatment with serine (25 µM) or HX630 (RXR agonist, 1 µM), prevented the increase of fragmented nuclei and apoptosis induced by BMAA, both in amacrine neurons and PHRs. In addition, preliminary results showed that BMAA induced ROS increase, which was reduced in presence of HX630. In the ARPE-19 cells, 10 µM BMAA induced cell death and decreased mitochondrial activity. Noteworthy, at different sub-lethal concentrations, BMAA induced alterations in mitochondrial morphology and distribution. These results suggest that BMAA induces subcellular changes affecting viability in both neurons and ARPE-19 cells, confirming BMAA as a threat to human health by inducing neurodegenerative damages. Furthermore, RXR receptor activation and serine supplementation exert a protective effect against BMAA toxicity in retinal neurons.