Macrophages modulate fibrosis during newt lens regeneration

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Georgios Tsissios - , Miami University (Autor:in)
  • Anthony Sallese - , Miami University (Autor:in)
  • J Raul Perez-Estrada - , Miami University (Autor:in)
  • Jared A Tangeman - , Miami University (Autor:in)
  • Weihao Chen - , Miami University (Autor:in)
  • Byran Smucker - , Miami University (Autor:in)
  • Sophia C Ratvasky - , Miami University (Autor:in)
  • Erika Grajales-Esquivel - , Miami University (Autor:in)
  • Arielle Martinez - , Miami University (Autor:in)
  • Kimberly J Visser - , Center for Regenerative Therapies Dresden (CRTD) (Autor:in)
  • Alberto Joven Araus - , Karolinska Institutet (Autor:in)
  • Hui Wang - , Miami University (Autor:in)
  • András Simon - , Karolinska Institutet (Autor:in)
  • Maximina H Yun - , Regeneration komplexer Strukturen bei erwachsenen Wirbeltieren (NFoG), Exzellenzcluster PoL: Physik des Lebens, Max Planck Institute of Molecular Cell Biology and Genetics (Autor:in)
  • Katia Del Rio-Tsonis - , Miami University (Autor:in)

Abstract

BACKGROUND: Previous studies have suggested that macrophages are present during lens regeneration in newts, but their role in the process is yet to be elucidated.

METHODS: Here we generated a transgenic reporter line using the newt, Pleurodeles waltl, that traces macrophages during lens regeneration. Furthermore, we assessed early changes in gene expression during lens regeneration using two newt species, Notophthalmus viridescens and Pleurodeles waltl. Finally, we used clodronate liposomes to deplete macrophages during lens regeneration in both species and tested the effect of a subsequent secondary injury after macrophage recovery.

RESULTS: Macrophage depletion abrogated lens regeneration, induced the formation of scar-like tissue, led to inflammation, decreased iris pigment epithelial cell (iPEC) proliferation, and increased rates of apoptosis in the eye. Some of these phenotypes persisted throughout the last observation period of 100 days and could be attenuated by exogenous FGF2 administration. A distinct transcript profile encoding acute inflammatory effectors was established for the dorsal iris. Reinjury of the newt eye alleviated the effects of macrophage depletion, including the resolution of scar-like tissue, and re-initiated the regeneration process.

CONCLUSIONS: Together, our findings highlight the importance of macrophages for facilitating a pro-regenerative environment in the newt eye by regulating fibrotic responses, modulating the overall inflammatory landscape, and maintaining the proper balance of early proliferation and late apoptosis of the iPECs.

Details

OriginalspracheEnglisch
Aufsatznummer141
FachzeitschriftStem cell research & therapy
Jahrgang15
Ausgabenummer1
PublikationsstatusVeröffentlicht - 14 Mai 2024
Peer-Review-StatusJa

Externe IDs

PubMedCentral PMC11094960
Scopus 85193206975

Schlagworte

Schlagwörter

  • Animals, Macrophages/metabolism, Regeneration/drug effects, Fibrosis, Lens, Crystalline/metabolism, Salamandridae, Apoptosis/drug effects, Cell Proliferation/drug effects