Retinal neuroinflammation in an ALS mouse model (SOD1G93A)

Abstract

Purpose : To determine the differences in retinal microglial and ganglion cell behaviour in a SOD1G93A mouse model (SOD) of amyotrophic lateral sclerosis (ALS) compared to the wild type (WT).

Methods : In retinal whole-mounts labelled with anti-Iba-1 (microglial marker) from two experimental groups WT (n=6) and SOD ALS (n=6), were quantified the number of retinal ganglion cells (RGCs) Brn3a+ and the signs of microglial activation in different retinal layers: i) Iba-1 + cells number in outer segments (OS), outer plexiform layer (OPL) and inner complex layer (ICL) constituted by inner plexiform layer (IPL), ganglion cell layer (GCL) and retinal nerve fiber layer (RNFL); ii) area occupied by Iba-1+ cells in OPL and IPL; and iii) arbor area of Iba-1+ cells in OPL and IPL. In addition, the expression of anti- IFN-γ and anti-IL-1β (pro-inflammatory M1 phenotype) and anti-arginase-I and anti-IL-10 (anti-inflammatory M2 phenotype) were analysed. Animals were sacrificed with 120 days old (advanced stage of the disease).

Results : Compared to WT, the retina of SOD1 ALS mice showed: i) Migrations and reorientation processes of some Iba-1 + cells; ii) a significant increase in the area occupied by each microglial cell in the total area of the retina; ii) a significant increase in arbor area in the outer plexiform layer (OPL) inferior sector; iii) 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) expression of IFN-γ and IL-1β; vii) non-expression of IL-10 and arginase-I; v) A decrease in number of RGCs.

Conclusions : In the SOD1G93A ALS model at 120 days (advanced stage of the disease), retinal microglial activation occurs, taking a pro-inflammatory M1 phenotype, which affected OPL and inner retinal layers and could be related to the RGCs loss. Although ALS is a disease of motor neurons, it can also affect retinal tissue, where an inflammatory process and death of retinal neurons occurs.

This is a 2021 ARVO Annual Meeting abstract.