Emil Kriukov, Anthony Mukwaya, Paul Francis Cullen, George Baldwin, Volha V Malechka, Nasrin Refaian, Nikita Bagaev, Everett Labrecque, Sthavir Vinjamuri, Milica A Margeta, Petr Baranov | bioRxiv | 2025
Abstract
Host retinal microglia and macrophage activation is a major barrier to donor neuron integration after transplantation. We found that transplantation of stem cell–derived retinal ganglion cells (RGCs) into adult mouse retinas triggered a shift in host myeloid cells from a homeostatic to a disease-associated microglia (DAM) profile, characterized by reduced Tmem119 and increased Apoe, Lgals3, and Spp1 expression. Single-cell transcriptomics and RNA velocity revealed dynamic, bi-directional transitions between activated and homeostatic states, suggesting that this response is reversible. These findings link transplant-induced myeloid activation to mechanisms seen in neurodegenerative diseases of the brain and eye.
