Retinal ganglion cell loss and microglial activation in a sod1g93a mouse model of amyotrophic lateral sclerosis

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Abstract

The neurodegenerative disease amyotrophic lateral sclerosis (ALS) affects the spinal cord, brain stem, and cerebral cortex. In this pathology, both neurons and glial cells are affected. However, few studies have analyzed retinal microglia in ALS models. In this study, we quantified the signs of microglial activation and the number of retinal ganglion cells (RGCs) in an SOD1G93A transgenic mouse model at 120 days (advanced stage of the disease) in retinal whole-mounts. For SOD1G93A animals (compared to the wild-type), we found, in microglial cells, (i) a significant increase in the area occupied by each microglial cell in the total area of the retina; (ii) a significant increase in the arbor area in the outer plexiform layer (OPL) inferior sector; (iii) the presence of cells with retracted processes; (iv) areas of cell groupings in some sectors; (v) no significant increase in the number of microglial cells; (vi) the expression of IFN-γ and IL-1β; and (vii) the non-expression of IL-10 and arginase-I. For the RGCs, we found a decrease in their number. In conclusion, in the SOD1G93A model (at 120 days), retinal microglial activation occurred, taking a pro-inflammatory phenotype M1, which affected the OPL and inner retinal layers and could be related to RGC loss.

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Rojas, P., Ramírez, A. I., Cadena, M., Fernández-Albarral, J. A., Salobrar-García, E., López-Cuenca, I., … Salazar, J. J. (2021). Retinal ganglion cell loss and microglial activation in a sod1g93a mouse model of amyotrophic lateral sclerosis. International Journal of Molecular Sciences, 22(4), 1–20. https://doi.org/10.3390/ijms22041663

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