Medications and surgery can help to slow the progression of some forms of the disease, but there is no cure at present. Unraveling which are the most critical mechanisms involved in glaucoma is unlikely to be achieved in studies which are limited to the clinically observable changes to the retina and optic nerve head that are seen in human glaucoma. Far more detailed and invasive studies are required, preferably in a readily available animal model. Recently, we have developed a model of glaucoma in rats through weekly injections of chondrotin sulfate in the eye anterior chamber. Acute or chronic intracameral injections of CS significantly increase IOP as compared with vehicle-injected eyes. Moreover, injections of CS for 6 or 10 weeks significantly decrease the electroretinographic activity as well as flash visual evoked potentials. After 10 weeks of ocular hypertension induced by CS, a significant loss of ganglion cell layer cells and optic nerve fibers occurs in eyes treated with CS. These results indicate that weekly intracameral injections of CS mimic central features of human primary open-angle glaucoma. Thus, this model could be a useful tool for understanding the pathogenic mechanisms involved in glaucomatous neuropathy, as well as for the development of new therapeutic strategies. The major risk factor for glaucoma is the increased intraocular pressure, and its pharmacological and/or surgical reduction slows down the progression of glaucomatous damage. However, lowering ocular hypertension does not completely stop damage progression, indicating risk factors other than IOP. It has been consistently suggested that an elevation of IOP evokes a variety of consequential events, including reduction in blood flow which leads to a partial ischemic insult. In that sense, several evidences support a localized vascular insufficiency leading to perfusion deficits of ocular structures, including the ONH, the retina, the choroid, and the retrobulbar vessels. Combined with high IOP, ischemic mechanisms can cause oxidative stress, reperfusion damage, and ultimately axon loss. Several animal and human studies have indicated that vascular dysregulation and ischemia play a role in glaucoma pathogenesis. Retinal ischemia develops when retinal blood flow is insufficient to match the metabolic needs of the retina, one of the highest oxygenconsuming tissues. Ischemia impairs retinal energy metabolism, and triggers a reaction cascade which can result in cell death. Oxidative stress, excitotoxicity, calcium influx, and others mechanisms acting in tandem are of considerable importance in retinal ischemic damage. Notably, most of these mechanisms are also involved in glaucomatous neuropathy. Although there is no effective treatment against retinal ischemic injury, it is possible to activate an endogenous protection mechanism by ischemic preconditioning. IPC requires a brief period of ischemia applied before ischemic injury, which does not Evofosfamide produce any significant damage per se, and induces tolerance to the subsequent severely damaging ischemic event.