Macrophages modulate fibrosis during newt lens regeneration

• Published in: bioRxiv : the preprint server for biology
• Main Authors: Tsissios, Georgios, Sallese, Anthony, Perez-Estrada, J Raul, Tangeman, Jared A, Chen, Weihao, Smucker, Byran, Ratvasky, Sophia C, Grajales-Esquivel, Erika, Martinez, Arielle, Visser, Kimberly J, Araus, Alberto Joven, Wang, Hui, Simon, Andras, Yun, Maximina H, Rio-Tsonis, Katia Del
• Format: Journal Article
• Language: English
• Published: United States 05.06.2023

Previous studies indicated that macrophages play a role during lens regeneration in newts, but their function has not been tested experimentally. Here we generated a transgenic newt reporter line in which macrophages can be visualized . Using this new tool, we analyzed the location of macrophages during lens regeneration. We uncovered early gene expression changes using bulk RNAseq in two newt species, and . Next, we used clodronate liposomes to deplete macrophages, which inhibited lens regeneration in both newt species. Macrophage depletion induced the formation of scar-like tissue, an increased and sustained inflammatory response, an early decrease in iris pigment epithelial cell (iPEC) proliferation and a late increase in apoptosis. Some of these phenotypes persisted for at least 100 days and could be rescued by exogenous FGF2. Re-injury alleviated the effects of macrophage depletion and re-started the regeneration process. Together, our findings highlight the importance of macrophages in facilitating a pro-regenerative environment in the newt eye, helping to resolve fibrosis, modulating the overall inflammatory landscape and maintaining the proper balance of early proliferation and late apoptosis.