Abstract
Purpose :
Tissue damage in the central nervous system elicits a robust inflammatory response, partly mediated by infiltrating immune cells including macrophages. Infiltrating macrophages are involved in the pathological process and fibrotic scar formation after optic nerve crush. We investigated whether macrophage depletion could ameliorate injury response and preserve retinal ganglion cell (RGC) function, which could provide new insights into traumatic optic nerve injury treatments.
Methods :
Macrophage Fas-induced apoptosis (MAFIA) transgenic mice and C57BL/6 mice underwent optic nerve crush. MAFIA mice were treated with AP20187 to deplete macrophages. Mice were sacrificed at different time points (7, 14, and 28 days) after optic nerve injury. Blood samples and histology were used to verify systemic macrophage depletion. Optic nerves and retina were immunostained for confocal microscopy analysis of macrophage infiltration and RGC survival. RGC function was measured by the pattern electroretinogram.
Results :
Our results demonstrate the application of AP20187 decreases systemic macrophage levels and reduces infiltration of macrophages in the optic nerve and retina after optic nerve crush. Macrophage depletion reduces fibrotic scar formation in the optic nerve and RGC function is preserved after injury.
Conclusions :
We demonstrate the optic nerve scar formation consists of infiltrating macrophages. Depletion of macrophages may be an important step towards axonal regeneration and functional recovery by reducing optic nerve scar formation.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.