Glaucoma is a chronic and progressive optic neuropathy representing one of the leading causes of irreversible blindness worldwide. While intraocular pressure reduction remains the only validated treatment, it is insufficient to halt disease progression in all cases. Neuroinflammation has emerged as a pivotal mediator underlying the onset and progression of retinal ganglion cell and axonal degeneration in glaucomatous disease. This review synthesizes current data on the role of resident immune cells in the retina and optic nerve head, describing their activation mechanisms and functional phenotypes. It also addresses the contribution of infiltrating circulating monocytes to the amplification of the local inflammatory response. These findings open novel therapeutic perspectives based on immunomodulation, including targeting of the NLRP3 inflammasome, TNF-α, TLRs, P2X7 receptor, APOE/TREM2 axis, and modulation of the microglial M1/M2 phenotypic balance. Taken together, this body of work argues for a broader, integrated view of glaucoma as a neuroinflammatory disease of the visual pathways, justifying the development of neuroprotective strategies targeting innate immunity. Beyond ocular structures, experimental data from rodent and non-human primate models, as well as clinical brain imaging data, demonstrate that neuroinflammation extends throughout the central visual pathways (retrobulbar optic nerve, lateral geniculate nucleus, superior colliculus, and visual cortex). This retinotopically organized central glial activation may drive neuronal degeneration and foster its contralateral propagation, though whether peripheral macrophage infiltration into the central visual pathways plays any role remains to be investigated.
Bastelica et al. (Mon,) studied this question.
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