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YUAN LIU, Huiyi Jin, Xiangxiang Liu, Mohamed Khodeiry, Richard K Lee; Hematogenous Macrophages Contribute to Fibrotic Scar Formation After Optic Nerve Crush. Invest. Ophthalmol. Vis. Sci. 2021;62(8):2271.
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To investigate the role of infiltrating hematogenous macrophages in optic nerve fibrotic scar formation and explore the potential effect of macrophage depletion in retinal ganglion cell (RGC) protection and optic nerve regeneration after traumatic injury.
Col1α1-GFP mice and C57BL/6 mice received clodronate encapsulated liposome injection to deplete hematogenous macrophage. Phosphate buffered saline (PBS) liposomes were used as injection vehicle control. Intravenous liposome injection was performed via the retro-orbital sinus 3 days prior to optic nerve crush (ONC) and 1, 4, and 7 after ONC. To further dissect the role of hematogenous and resident macrophages in scar formation, we used Dil liposomes to label hematogenous macrophages. Immunofluorescence staining was used to characterize fibrotic scar after macrophage depletion and differentiate the role of hematogenous macrophage and resident microglia.
Hematogenous macrophages accumulated centrally in the fibrotic scar at the optic nerve crush site, while resident microglia were present at the edge of the scar. Hematogenous macrophage depletion reduced fibrotic scar formation in both Col1α1-GFP mice and C57BL/6 mice. The spindle-shaped optic nerve fibrotic scar was not present in the macrophage depleted treated group compared to the control-treated group. Macrophage depletion did not protect RGCs in the retina after traumatic optic nerve injury.
We characterized the fibrotic scar which forms after traumatic optic nerve crush and demonstrates that optic nerve scar formation is dependent on the infiltration of hematogenous macrophages. Depletion of hematogenous macrophages may be the first step towards axonal regeneration and functional recovery by reducing optic nerve scar formation.
This is a 2021 ARVO Annual Meeting abstract.
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