Szczepan, Manon and Llorian-Salvador, Maria and Yi, Caijiao and Hughes, David and Mack, Matthias and Chen, Mei and Xu, Heping (2025) Differential Roles of Macrophages and Microglia in Subretinal Fibrosis Secondary to Neovascular Age-Related Macular Degeneration. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 66 (3): 41. ISSN 0146-0404, 1552-5783
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PURPOSE. To investigate the differential role of infiltrating CCR2+ macrophages and CX3CR1+ microglia in neovascular AMD (nAMD)-mediated subretinal fibrosis. METHODS. Subretinal fibrosis was induced using the two-stage laser protocol in C57BL/6J or CX3CR1gfp/+ mice. The fibrotic lesion was detected using collagen-1 staining in retinal pigment epithelial /choroidal flatmounts. Infiltrating macrophages and microglial were identified using F4/80, CCR2, and CX3CR1 markers at one, three, six, and 10 days after the second laser. Circulating CCR2+ monocytes were depleted using the MC-21 antibody, whereas CX3CR1+ microglia were depleted using PLX5622. BV2 microglia were treated with TGF-beta 1 for 96 hours, and their profibrotic potential was examined by quantitative PCR and immunocytochemistry. RESULTS. Subretinal fibrosis lesions developed three days after the second laser, accompanied by persistent CCR2+F4/80+ macrophage and CX3CR1+ cell infiltration. Inflammation in the first three days after the second laser was dominated by filtrating CX3CR1+ cells, and the number increased until day (D) 10 post-second laser. Depletion of CCR2+ monocytes from D5-10 significantly reduced the vascular and fibrotic components of the lesion, while CX3CR1+ cell depletion reduced Isolectin B4+ but not collagen-1+ lesion size. Bone marrow-derived macrophages from D6 and D10 mice expressed significantly higher levels of alpha-smooth muscle actin (alpha-SMA) and collagen-1 compared to cells from D1 and D3. TGF beta 1 treatment increased TMEM119, CX3CR1, IL1b and iNOS gene expression but did not affect Acta2 and Col1a1 gene expression in BV2 cells. CONCLUSIONS. CCR2+ monocytes, but not CX3CR1+ microglia, critically contribute to the development of subretinal fibrosis in nAMD.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CHOROIDAL NEOVASCULARIZATION; ACCUMULATION; INFLAMMATION; inflammation; microglia; retinal fibrosis; wound healing; angiogenesis |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 02 Jun 2026 11:59 |
| Last Modified: | 02 Jun 2026 11:59 |
| URI: | https://pred.uni-regensburg.de/id/eprint/67381 |
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