AbstractPurpose To review our results of experiments relating to neuroprotective therapy of glaucoma at various levels of the visual pathway.Methods Using isolated retinal ganglion cell (RGC) culture system, drug effects on hypoxic stress‐induced damage of RGCs were studied. Using monkey unilateral experimental glaucoma model, 1) drug effects on the optic nerve head (ONH) circulation, and 2) neural degeneration secondary to experimental glaucoma in the CNS visual pathway were studied. Drug effects on CNS degeneration secondary to RGC death were also studied in a mice model. A double‐masked placebo‐controlled trial was conducted to investigate the effect of oral nilvadipine, a Ca2+‐blocker, on the visual field in normal tension glaucoma (NTG) patients.Results Ca2+‐blockers and some of the beta‐blockers were found to be neuroprotective against hypoxia‐induced cultured RGC damage. Both nilvadipine and lomerizine, another Ca2+‐blocker, increased the ONH circulation not only in normal, but also experimental glaucoma eyes in monkeys. In the lateral geniculate nucleus (LGN) of experimental glaucoma monkeys, M‐cells were first damaged, and then both M‐ and P‐cells damaged, where endoplasmic reticulum (ER) stress in apoptotic processes and activation of glial cells were involved. Systemic lomerizine and memantine were found to alleviate CNS damages secondary to NMDA‐induced RGC death in mice. In a clinical trial, a low dose of oral nilvadipine (4mg/day) significantly decreased the rate of mean deviation (MD) deterioration in NTG patients as compared to placebo.Conclusion A systemic drug administration such as oral nilvadipine which can alleviate damage at various levels of visual pathway may have potential in neuroprotective therapy in glaucoma.