Fig. 8

Summary of findings and proposed model identifying a role of secreted IgM in retinal maintenance during aging. This study highlights the contribution of secreted IgM in the maintenance of retinal health during aging. During normal aging, we observed a minor loss of retinal neurons, accompanied by a slight increase in activated microglia, which appear to be effectively modulated by resident Müller glia. In µs-/- mice lacking secreted IgM, we noted significant neurodegeneration during aging, along with an increase in apoptotic cells. These observations suggest a potential role for IgM in facilitating the clearance of apoptotic debris from the retina, consistent with its established function in immune regulation elsewhere in the body. Additionally, we observed alterations in the retinal cytokine profile in the absence of secreted IgM, characterized by elevated levels of pro-inflammatory cytokines and a marked reduction in anti-inflammatory cytokines, compared to the relatively balanced profile observed in aging WT mice. This pro-inflammatory shift in the absence of IgM was accompanied by significant reactive gliosis in some resident Müller glia. Together, these findings indicate that secreted IgM may contribute to retinal homeostasis during aging by modulating inflammatory responses and maintaining a supportive environment for neuronal health. Future studies will be necessary to further define the mechanisms underlying these observations and to explore the role of IgM in retinal health during advanced aging. Created in BioRender. Webster, S. (2024) BioRender.com/r68o468