Abstract
Purpose :
Following optic nerve damage, interleukin-1 (IL-1) is rapidly upregulated, initiating a cascade of immune responses. This includes the activation and recruitment of microglia and macrophages to the injury site, where they release additional inflammatory mediators, amplifying the immune response. We investigated the expression of IL-1 at the optic nerve injury site and whether interleukin-1 alpha (IL-1α) and interleukin-1 receptor type 1(IL-1r1) treatment could modulate the response to injury and conserve function of retinal ganglion cells (RGCs). This could provide novel insights into treating traumatic optic nerve injuries.
Methods :
IL-1α knockout (KO) mice, IL-1r1 KO mice and control C57BL/6 mice underwent optic nerve crush. Mice were euthanized at different time points (7, 14, and 28 days) following optic nerve injury. Confocal microscopy was utilized for immunostaining of optic nerves and retina to investigate scar formation and survival of RGC. Pattern electroretinography assessed RGC function.
Results :
Mice lacking IL-1r1 and IL-1α exhibited a reduced quantity of infiltrating CD68-positive macrophages in the nerve in comparison to C57BL/6 mice 14 days post-crush injury. Furthermore, IL-1r1 KO mice displayed a diminished size of the Glial Fibrillary Acidic Protein (GFAP) negative scar area at the optic nerve injury site.
Conclusions :
We demonstrate that the absence of IL-1 signaling, by deletion of IL-1r1 or IL-1α, leads to a significant reduction in macrophage infiltration and decreased scar formation following optic nerve injury. These findings suggest that interventions targeting IL-1 signaling pathways could provide novel approaches to managing traumatic optic nerve injuries.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.