神经退行性病

    Amyotrophic lateral sclerosis, a neurodegenerative motor neuron disease with retinal involvement
  • Figure 1|Main changes observed in microglial cells and RGC in the ALS model SOD1G93A at a very advanced stage of the disease (120 days). 

    The activation of microglial cells in retinas with ALS has been poorly studied. There are only three works on this topic, and they are performed in different animal models of ALS (Ringer et al., 2017; Cho et al., 2019; Rojas et al., 2021). In the mouse model of ALS, devoid of ran2-binding protein (Ranbp2), activation of CD11b+ and CD45+ microglial cells was observed. In addition, an increase in the number of F4/80+ microglia and the presence of amoeboid microglial forms were also found (Cho et al., 2019). In the SOD1G93A mouse model, using anti-Iba-1 (microglia-specific marker) in the retinal sections, Ringer et al. (2017) found no activation of microglial cells in either the early or late stages of the disease. However, in a recently published study in the SOD1G93A mouse model at an advanced time of disease (120 days), signs of microglial activation were found. The difference between this study with respect to the one mentioned above is that it was performed on retinal whole-mounts, which allow for a more detailed morphological study of microglial cells. Microglial changes were recorded in the main retinal layers where the microglia were located, such as the outer plexiform layer and the inner retinal layer complex (comprising the inner plexiform layer and the nerve fiber layer–ganglion cell layer). These changes were characterized by a significant increase in the area of microglial arborization, a significant increase in cell area, the appearance of cells with retracted processes, and cell displacements and clustering (Figure 1; Rojas et al., 2021). Furthermore, in this study, microglial cells were shown to be of the M1 activation phenotype, as they expressed interferon gamma and IL-1β, which are typical markers of the M1 (proinflammatory-cytotoxic) response (Figure 1), while they were not labeled with antibodies typical of the M2 (anti-inflammatory-neuroprotective) response, such as arginase-I and IL-10 (Rojas et al., 2021). In addition, the loss of retinal ganglion cells was also observed in these animals (Figure 1), consistent with the damage observed in these cells in other ALS models (Volpe et al., 2015; Cho et al., 2019). All this would indicate that not only motor neurons, but also retinal neurons, are affected by ALS (Rojas et al., 2021). The results of this study demonstrate that, in the SOD1G93A ALS model, at an advanced stage of the disease, the microglial cells are of the proinflammatory-cytotoxic M1 phenotype, which could induce neuronal death, as evidenced by the loss of retinal ganglion cells (Figure 1). This would be in line with the findings with regard to the spinal cord, where microglia in the late stages of the disease are present in an M1 phenotype (Liao et al., 2012), thus indicating that the changes occurring at the spinal cord or brain level are occurring in parallel in the retina.


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  • 发布日期: 2021-12-08  浏览: 507
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