Modulation of microglia activation after human donor retinal ganglion cell transplantation

Stem cell-derived retinal ganglion cell (RGC) transplantation therapy offers a promising avenue for restoring vision in patients with significant RGC loss. The major challenge in this therapeutic approach is ensuring the survival of transplanted human donor RGCs within the host retina. Previously, we demonstrated the pivotal role of host retinal microglia and macrophages in the acceptance and survival of human donor cells. This current study aimed to improve the survival and integration of human donor RGCs through modulation of the host retinal microglia. Pretreatment of human donor RGCs with annexin V and soluble FasL (sFasL) before transplantation significantly enhanced their acceptance and survival rate. Detailed analyses of the host mouse retina post- transplantation revealed morphological changes and activation patterns in microglia and macrophages. These findings indicate that sFasL and annexin V activate pro-survival pathways and foster a supportive environment for the acceptance and survival of transplanted human donor RGCs.