The role of monocytes in optic nerve injury

Abstract

Monocytes, including monocyte-derived macrophages and resident microglia, mediate many phases of optic nerve injury pathogenesis. Resident microglia respond first, followed by infiltrating macrophages which regulate neuronal inflammation, cell proliferation and differentiation, scar formation and tissue remodeling following optic nerve injury. However, microglia and macrophages have distinct functions which can be either beneficial or detrimental to the optic nerve depending on the spatial context and temporal sequence of their activity. These divergent effects are attributed to pro- and anti-inflammatory cytokines expressed by monocytes, crosstalk between monocyte and glial cells and even microglia-macrophage communication. In this review, we describe the dynamics and functions of microglia and macrophages in neuronal inflammation and regeneration following optic nerve injury, and their possible role as therapeutic targets for axonal regeneration.

Keywords: fibrotic scar; glial scar; inflammation; macrophage; microglia; optic nerve injury; regeneration.

Figure 1

Scar formation after optic nerve injury. Diagram depicting the events of scar formation after optic nerve crush injury in mice. Phase I (within 3 days post-injury): early after optic nerve injury, cell death occurs within the lesion site and axons are damaged. Microglia respond by secreting cytokines and chemokines. Macrophages begin to migrate to the injury site (not shown). Phase II (3–10 days post-injury): macrophages infiltrate the lesion core and perivascular fibroblasts accumulate at the injury site, microglia and astrocytes react around the lesion core. Phase III (after 10 days post-injury): by 10 days after optic nerve injury, the scar has matured: glial scar (consisting of microglia and astrocytes) and fibrotic scar (consisting of fibroblasts and macrophages).

Figure 2

Schematic illustration of the numbers of reactive monocytes at the injured site and the time course of multicellular responses to optic nerve injury. Above: Microglia response to an optic nerve injury within 24 hours and peak at 2–3 days post-injury (green). Macrophages infiltrate to the lesion site at around 3 days post-injury and peak at 1 week post-injury. Pro-inflammatory macrophages are the 1^st wave of macrophage infiltration (yellow). The 2^nd wave of macrophage influx is comprised by anti-inflammatory macrophages (red). Below: Multicellular responses, function of monocytes and neural inflammation during different phases post optic nerve injury. ECM: Extracellular matrix.