Background Glaucoma is one of the leading causes of irreversible blindness in the world. flat-mounted retina demonstrated peripheral RGC loss associated with tissue macrophage/microglia activation (CD68+). Gene expression analysis of hypertensive and normotensive retinas revealed a significant increase of pro-inflammatory genes such as CCL2, IL-1, and Nox2 mRNA expression compared to na?ve eyes. Importantly, we found an upregulation of pro-inflammatory markers such as IL-1 and TNF and astrocyte and tissue macrophage/microglia activation in hypertensive and normotensive RGC projection sites in the SCs compared to a na?ve SC. To understand how GS-1101 neuroinflammation in the hypertensive retina is sufficient to damage both right and left SCs and the normotensive retina, we used an inflammatory GS-1101 model consisting in an unilateral stereotaxic injection of TNF (25?ng/l) in the GS-1101 right SC of na?ve rats. Two weeks after TNF injection, using an optomotor test, we observed that rats had visual deficiency in both eyes. Furthermore, both SCs showed an upregulation of genes and proteins for astrocytes, microglia, and pro-inflammatory cytokines, notably IL-1. In addition, both retinas exhibited a significant increase of inflammatory markers compared to a na?ve retina. Conclusions All these data evidence the complex role played by the SCs in the propagation of neuroinflammatory events induced by unilateral ocular hypertension and provide a new insight into the spread of neurodegenerative diseases such as glaucoma. matching … Ocular hypertension induces retinal inflammation and tissue macrophage activation in HT and NT eyes An earlier study showed that in an unilateral laser-induced OHT, the NT eye is also altered [20]. We aimed to explore and further detail this new data in our experimental model of OHT. In all experiments, we compared the EVC and contralateral structures to the na?ve structures. EVC resulted in astrocyte activation (GFAP, show colocalization between markers. Scale … Discussion In this study, we used an experimental model of glaucoma (induced by EVC), which is very close to the human form of the disease. Numerous studies have characterized and used this EVC model, which matches specific glaucoma symptoms: IOP increase with a reduction of aqueous humor outflow, progressive RGC degeneration, aqueous humor TGF-2 level increase, and trabecular cell death [2, 3, 32]. The EVC model used in this study shares several features with human primary open-angle glaucoma, but it is known there is blood flow damage. Indeed, following episcleral/vortex veins cauterization, arterial blood is suddenly left with insufficient outflow from the globe. This would rapidly produce significant ocular venous congestion, which is consistent with an immediate rise in IOP observed in this ocular hypertensive model [33]. In this EVC glaucoma model, RGC loss is progressive (22?% decrease in peripheral retina 6?weeks after cauterization). This peripheral RGC loss has also been observed in different glaucoma models with, however, a markedly different percentage of RGC loss. One study reports an 11?% decrease ROC1 of RGC density 12?weeks after intracameral microbead injection in mice GS-1101 [34], while another group showed a 30?% decrease 4?months after an association of microbead injection and laser photocoagulation of the trabeculum meshwork in mice [35]. Other groups have developed EVC model but in other rat strains. Thus, one study reported 15?% of RGC loss in peripheral retina 8?weeks after EVC. In another study, the authors found a decrease of 40?% in RGC density 26?weeks after EVC [36], whereas two other groups observed, 7?weeks after EVC, 30?% of RGC loss in peripheral retina [37] and in the whole of the retina for the other [38], respectively. In neurodegenerative disease, a neuronal degeneration is almost always associated with inflammation. Therefore, in glaucomatous human eyes, an activated phenotype of astrocytes, Mller cells and microglia cells are found in retinal layers [39]. Indeed, the hallmarks of glial and microglial activation such as cellular.