Apoptosis at the optic fissure shapes transient retinal myeloid states
- 1University of Utah
Abstract
Microglia and CNS-associated macrophages (CAMs) originate from yolk sac erythromyeloid progenitors, yet the process that mediates their colonization of the mammalian eye and the developmental cues that promote their diversification remain unclear. Here, we identify the optic fissure as the primary entry site for myeloid cells into the embryonic mouse retina. This entry is spatially and temporally coupled with a localized wave of cell death. This apoptotic niche contains colonizing myeloid cells in a transient CD206+ state, and apoptotic burden directly correlates with CD206 expression across development. We find that disrupting apoptotic recognition pathways, specifically Cx3cr1 and Itgam, promotes enrichment of CD206+ cells; likewise, increasing cell death via genetic loss of Atoh7 results in elevated CD206+ population, indicating that impaired clearance and increased death converge on a common outcome within a constrained developmental window. Both CD206+ and CD206- subsets contribute to phagocytosis during optic fissure closure, indicating that CD206 expression does not mark a specialized phagocytic subset. Intriguingly, unlike parenchymal microglia, CD206+ cells are selectively spared from pharmacological CSF1R inhibition, revealing distinct survival requirements within the fissure niche. Together, these findings indicate that localized apoptotic niches encountered during myeloid cell entry influence the initial states and properties of CNS-resident myeloid cells.
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BibTeX
@misc{ghena2026apoptosis,
title = {{Apoptosis at the optic fissure shapes transient retinal myeloid states}},
author = {N. Ghena and W. S. Warner and Y. Landaverde Rodriguez and J. Schwakopf and J. M. Roberts and M. L. Vetter},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.06.757121},
url = {https://www.biorxiv.org/content/10.64898/2026.10.06.757121v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Apoptosis at the optic fissure shapes transient retinal myeloid states
AU - N. Ghena
AU - W. S. Warner
AU - Y. Landaverde Rodriguez
AU - J. Schwakopf
AU - J. M. Roberts
AU - M. L. Vetter
PY - 2026
DA - 2026/10/06
PB - bioRxiv
DO - 10.64898/2026.10.06.757121
UR - https://www.biorxiv.org/content/10.64898/2026.10.06.757121v1
AB - Microglia and CNS-associated macrophages (CAMs) originate from yolk sac erythromyeloid progenitors, yet the process that mediates their colonization of the mammalian eye and the developmental cues that promote their diversification remain unclear. Here, we identify the optic fissure as the primary entry site for myeloid cells into the embryonic mouse retina. This entry is spatially and temporally coupled with a localized wave of cell death. This apoptotic niche contains colonizing myeloid cells in a transient CD206+ state, and apoptotic burden directly correlates with CD206 expression across development. We find that disrupting apoptotic recognition pathways, specifically Cx3cr1 and Itgam, promotes enrichment of CD206+ cells; likewise, increasing cell death via genetic loss of Atoh7 results in elevated CD206+ population, indicating that impaired clearance and increased death converge on a common outcome within a constrained developmental window. Both CD206+ and CD206- subsets contribute to phagocytosis during optic fissure closure, indicating that CD206 expression does not mark a specialized phagocytic subset. Intriguingly, unlike parenchymal microglia, CD206+ cells are selectively spared from pharmacological CSF1R inhibition, revealing distinct survival requirements within the fissure niche. Together, these findings indicate that localized apoptotic niches encountered during myeloid cell entry influence the initial states and properties of CNS-resident myeloid cells.
ER -