## 4 Discussion  
The loss of ganglion cells in glaucoma eventually leads to blindness. In the case of open-angle glaucoma, blockage of the trabecular meshwork impedes the outflow of aqueous humor [48; 49; 50]. There are several characteristics of M/N cells that led us to investigate their behavior in a mouse model of glaucoma. First, they are activated in response to a variety of perturbations in homeostasis, including hypoxia, cell death, incisional and abrasion injuries, and cancer [37; 38; 39; 41; 46; 51; 52]. Under these conditions, they rapidly accumulate in areas of stress and within wounds. Following injection of microbeads into the AC, M/N cells increase in number in the trabecular meshwork, canal of Schlemm, cornea, and GCL. Brain-derived M/N cells injected into the AC accumulated in the same areas as the endogenous M/N cells. The presence of beads, elevation in IOP, and subsequent tissue damage are likely stimuli for the activation of endogenous M/N cells and homing of both populations of M/N cells to areas of compromise throughout the eye. However, the addition of exogenous cells prevented an increase in endogenous cells in the trabecular meshwork when compared to the no treatment and vehicle control groups in glaucomatous eyes. Apart from the trabecular meshwork, the total number of M/N cells (both exogenous and endogenous) almost doubled compared to the no treatment and vehicle control groups in response to elevated IOP. It is possible that the phagocytosed magnetic beds triggered apoptosis in the M/N cells, thereby lowering their number in this region. The increased number of endogenous Myo/Nog cells in the cornea after injection is probably due to the stress that the injection causes in this tissue and the acute increase in IOP forcing the corneal tissue to stretch, as well as being the location of the injection. Importantly, M/N cells participated in the clearance of microbeads. M/N cells also ingest fattoo ink in the skin and dead cells in the lens and retina [37; 43; 53]. We also reported that M/N cells engulf microbeads injected into the AC [53]. It is possible that there were too many beads to clear, even with M/N cell supplementation, to significantly reduce IOP. Furthermore, the polystyrene beads, like fattoo ink, may remain within the cytoplasm of M/N cells once internalized. Another important characteristic of M/N cells relevant to this study is their ability to protect photoreceptors in oxygen-induced retinopathy and from light damage [38; 39]. Their migration to focal wounds in the brain also mitigated cell death [46]. In this mouse model of glaucoma, exogenous M/N cells reduced RGC loss and preserved GCL-NFL thickness in the absence of a significant reduction in IOP. M/N cells' mitigation of RGC loss appears to reflect a neuroprotective effect within the retina, as opposed to a significant drop in IOP, and suggests that their mediation of neuroprotection involves the release of factors within the vitreous and/or the retina itself. Although we assessed RGC numbers using their morphology and nuclear size, we did not label RGCs with a specific antibody against them. Hence, it is possible that in some of the counts that we carried out, Myo/Nog cells, microglia, or astrocytes could have been mistakenly counted. However, the numbers of most of these will increase in stressed tissue. The reduction in cell numbers in the GCL caused by M/N cell injection indicates that it reduced the level of stress in that layer and, likely, the overall number of ganglion cells. M/N cells' mitigation of RGC loss in this model of glaucoma is predicted to involve multiple mechanisms, including the regulation of the BMP signaling pathway via the release of Noggin. M/N cells are the primary, if not exclusive, source of Noggin throughout the embryo and all adult tissues studied thus far [30; 36; 37; 38; 39; 40; 43; 45; 46]. Their release of Noggin is critical for normal development of the central nervous system and the eyes [30; 36; 51].