Evaluating the Evidence for Neuroprotective and Axonal Regenerative Activities of Different Inflammatory Cell Types After Optic Nerve Injury

Abstract

The optic nerve contains retinal ganglion cell (RGC) axons and functions to transmit visual stimuli to the brain. Injury to the optic nerve from ischemia, trauma, or disease leads to retrograde axonal degeneration and subsequent RGC dysfunction and death, causing irreversible vision loss. Inflammatory responses to neurological damage and axonal injuries in the central nervous system (CNS) are typically harmful to neurons and prevent recovery. However, recent evidence indicates that certain inflammatory cell types and signaling pathways are protective after optic nerve injury and promote RGC survival and axonal regeneration. The objective of this review is to examine the evidence for diverse effects of inflammatory cell types on the retina and optic nerve after injury. Additionally, we highlight promising avenues for further research.

Keywords: Axonal regeneration; Macrophage; Microglia; Muller glia; Neuroinflammation; Optic nerve.

Fig. 1

Schematic diagram illustrating different inflammatory cell types within the retina and optic nerve following optic nerve injury. Astrocytes, microglia, macrophages, and neutrophils exist within both the retina (a) and optic nerve (b), while Muller glia are localized only in the retina (a), and oligodendrocytes are limited to the optic nerve (b). Secretion of various molecular mediators including cytokines, chemokines, growth factors, and myelin-derived inhibitory proteins modulate pro-regenerative or pro-inflammatory effects. Refer to Table 1 for examples of secreted neuroprotective and regenerative factors by each cell type. Changes in cellular morphologies upon activation are not indicated. See text for further details. Pro-regenerative signaling is indicated by green arrows and pro-inflammatory/neurotoxic signaling is indicated by red lines. RGC: retinal ganglion cell