Although IPC confers a highly significant neuroprotection in different in vitro and in vivo models of ischemia, its utilization as a clinical strategy is mostly limited because the onset of retinal ischemia is largely unpredictable, in contrast to the onset of Bortezomib reperfusion that could be more predictable. In this vein, another endogenous form of ischemic protection, in which a short series of repetitive cycles of brief ischemia/reperfusion are applied immediately at the onset of reperfusion, termed postconditioning, has been reported in several tissues. Recently, we have shown that a 7-min pulse of ischemia applied 5 min after the reperfusion onset, induces an almost complete histological and functional protection in eyes exposed to ischemic injury. Based on the highly effective protection induced by IPC and PostC against an acute ischemic episode, the aim of this work was to analyze the effect of brief ischemia pulses on retinal damage induced by experimental glaucoma. The present results indicate that a weekly application of 5-min retinal ischemia pulses which showed no effect per se, abrogated functional and histological alterations induced by chronic ocular hypertension. Notably, the retinal protection induced by ischemia pulses was independent from ocular hypertension, as shown by the fact that ischemia pulses did not affect the increase in IOP induced by CS injections. Human open angle glaucoma is a progressive optic neuropathy. In agreement, we have identified different stages in the experimental model of glaucoma induced by weekly injections of CS, that show the following characteristics. In order to assess whether the induction of ischemic tolerance was able to reduce glaucoma progression, the application of ischemia pulses started at 6 weeks of treatment with CS, a time point in which functional alterations are already evident. Several observations support that some components of the flash ERG and VEPs can be affected in experimental models of glaucoma. The weekly application of ischemia pulses, which did not show any effect in control retinas, prevented the decrease in the ERG a- and b-wave and flash VEP N2-P2 amplitude induced by chronic ocular hypertension, supporting that the induction of ischemic tolerance not only preserved the retinal function, but also the activity of all cells in the pathway from photoreceptors to visual cortex, including RGCs and their axons. In addition to RGCs, the GCL is comprised of a number of displaced amacrine cells. NeuN is a DNA-binding protein that identifies most mature neuronal populations, which has been used as a specific marker for RGCs, while Thy-1 is a surface glycoprotein uniquely expressed in RGCs. In the retina from eyes injected with CS without ischemia pulses, a significant loss of GCL cells, as shown by H&E and DAPI staining, and NeuN and Thy-1 immunohistochemistry was observed, without changes in IPL, INL, OPL, and ONL thickness. Ischemia pulses significantly reduced the effect of ocular hypertension on the number of cells in the GCL, as well on the number of apoptotic cells in the GCL. In addition, a significant decrease in the axon number was evident in hypertensive eyes without ischemia pulses.