PUBLICATION

Macrophage/microglia-dependent mechanisms drive retinal pigment epithelium regeneration in zebrafish

Authors
Leach, L.L., Gonzalez, R.G., Jayawardena, S.U., Gross, J.M.
ID
ZDB-PUB-250921-1
Date
2025
Source
Cell Reports   44: 116325116325 (Journal)
Registered Authors
Keywords
CP: Immunology, CSF1R, interleukin-34, macrophage, microglia, regeneration, retinal pigment epithelium, zebrafish
MeSH Terms
  • Animals
  • Macrophages*/metabolism
  • Microglia*/metabolism
  • Phagocytosis
  • Regeneration*
  • Retinal Pigment Epithelium*/physiology
  • Zebrafish*/physiology
PubMed
40974576 Full text @ Cell Rep.
Abstract
The retinal pigment epithelium (RPE) surrounds the posterior eye and maintains the health and function of the photoreceptors. Consequently, RPE dysfunction or damage has a devastating impact on vision. Due to complex etiologies, there are currently no cures for patients with RPE degenerative diseases, which remain some of the most prevalent causes of vision loss worldwide. Further, owing to a limited capacity for mammalian tissue repair, we know little about how the RPE regenerates. Here, we utilize zebrafish to uncover mechanisms driving intrinsic RPE regeneration. We show that microglia are indispensable for repair and present evidence that supports the role of interleukin-34 in recruiting macrophages/microglia to the RPE injury site. Further, we identify aberrant RPE injury site debris accumulation due to decreased macrophage/microglia localization, and we find that phagocytosis is an important mechanism driving debris clearance. Together, our results identify new regenerative functions of macrophages/microglia after RPE damage.
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