Abstract
Purpose :
Recent studies show macrophages play a complex and crucial role in neuroinflammation, neuronal survival, and tissue repair. This study investigated the role of macrophages in optic nerve injury response, fibrotic scar formation, and retinal ganglion cell (RGC) function by selectively depleting macrophages in macrophage Fas-induced apoptosis (MaFIA) mice.
Methods :
Macrophage Fas-induced apoptosis (MaFIA) transgenic mice and control C57BL/6 mice were used in this study. Mice optic nerve were crushed on day 0. MaFIA mice were intraperitoneally injected with AP20187 for 5 days to activate Fas and deplete macrophages (CD68+) via apoptosis. Mice were sacrificed on day 14 after optic nerve injury. Histology and immunostaining of spleens and livers were used to verify organ macrophage depletion. Optic nerves were immunostained for confocal microscopy analysis of macrophage depletion. RGC function was measured by pattern electroretinography (PERG).
Results :
AP20187 injection in MaFIA mice depleted a large number of macrophages in the liver, spleen, and optic nerve. Depleting macrophages significantly decreased the formation of fibrotic scars in MaFIA mice areas of optic nerve crush compared to C57BL/6 mice. In MaFIA mice, depleting CD68+ macrophages preserved the function of RGCs up to two months post-injury.
Conclusions :
This study has revealed the neuroprotective effects of macrophage depletion using MaFIA mice. Macrophage depletion or modulation of function may be a novel therapeutic approach to optic nerve injury, contributing to the broader goal of improving neural regeneration and functional recovery in CNS disorders.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.