Abstract
BACKGROUND: The damage and regeneration of retinal ganglion cells (RGCs) have been extensively studied. Among them, immune cells in different parts of the visual pathway play an important role in injury, regeneration and repair, but a comprehensive analysis of their spatial and temporal distribution is lacking. PURPOSE: This review emphasizes the unique characteristics of immune cells within the visual input pathway, focusing on their spatiotemporal dynamics in the retina, optic nerve head (ONH), and optic nerve during glaucoma and traumatic optic nerve injury. METHODS: A comprehensive search was conducted across PubMed and Web of Science up to April 2025. Studies were included if they reported immune cells under glaucoma or optic nerve crush (ONC) animal models. FINDINGS: Each region of the visual input pathway displays a distinct immune cell composition, including Müller cells, microglia, astrocytes, T cells, and oligodendrocytes, all of which work together to maintain homeostasis and respond to injury. Some immune cells are specific to certain regions, while others are shared across areas. Furthermore, even within a single glial cell type, there are different subtypes with unique developmental origins or marker profiles, reflecting a range of functions. In both glaucoma and traumatic optic nerve injury, retinal immune cells are rapidly activated, regardless of whether the initial impairment occurs in the soma or axon of RGCs, in the subacute or chronic course. The early stages of injury also see the presence of adaptive immune cells, such as T cells and neutrophils. Macrophages and microglia typically play complementary roles, while astrocytes show prolonged activation compared to microglia in the optic nerve, though this pattern does not hold in the retina following ONC. CONCLUSIONS: Understanding the spatiotemporal dynamics of these immune responses in glaucoma and traumatic optic nerve injury is crucial for developing targeted therapies that can reduce RGC loss, mitigate neurotoxicity, and promote functional recovery, ultimately preventing vision impairment. Targeting specific immune cell subsets may provide new strategies for delaying RGC damage.