Retinal neurodegeneration and neuroinflammation in a SOD1 mouse model of ALS

Abstract

AbstractPurposeTo determine in a SOD1G93A mouse model (SOD1) of amyotrophic lateral sclerosis (ALS) i) the changes in retinal ganglion cells (RGC) compared to the wild type (WT), and ii) establish whether the microglial activation previously observed in this model corresponds to an M1 or proinflammatory or M2 or anti‐inflammatory microglial phenotype.MethodsIn retinal whole‐mounts of 120‐day‐old animals, from two experimental groups WT (n = 6) and SOD ALS (n = 6), we studied i) the number of RGC with anti‐Brn3a+, and ii) the expression by microglia, labelled with anti‐Iba‐1, of M1 phenotype markers (anti‐IL‐1β and anti‐IFN‐γ) and M2 phenotype markers (anti‐arginase‐I and anti‐IL‐10).ResultsCompared to WT, the retina of SOD1 ALS mice showed: i) a decrease in the number of RGCs, ii) expression by microglia of IFN‐γ and IL‐1β; iii) non‐expression by microglia of IL‐10 and arginase‐I.ConclusionsThese findings demonstrate that in an ALS SOD1model, in an advanced stage of the disease, retinal microglial activation takes place, resulting in a proinflammatory M1 phenotype, which could be related to the loss of RGC. Although ALS is a disease of motor neurons, it can also affect retinal tissue, where a neuroinflammatory and neurodegenerative processes occur.