The characteristic loss of visual field due to
glaucoma is directly associated with retinal ganglion cell (RGC) death. The process of RGC death is thought to be biphasic, starting with a primary injury, followed by a slow secondary degeneration.
Retinal ischemia may establish the cellular conditions that create a fatal biochemical cascade;
hypoxia, followed by high excitotoxic levels of
glutamate cause pathologically elevated levels of intracellular
calcium resulting in neuronal cell death via apoptosis or
necrosis. Impaired ocular perfusion, primarily due to abnormal autoregulation and/or vasoconstriction caused by
endothelin-1, probably contributes to the ischemic milieu. Neuroprotection, the preservation of neurons that were either not damaged or only slightly damaged during the primary insult, has become important for the clinician when considering treatment options. Unoprostone, the first synthetic docosanoid, has been demonstrated to exhibit neuroprotective properties. In an ischemic animal model, unoprostone protected RGCs in a dose-dependent manner. Unoprostone inhibits
glutamate stimulation and opens
maxi-K channels, which are
potassium channels that reach an activation threshold only during depolarization and/or at high intracellular Ca2+ concentrations. The resultant large efflux of K+ hyperpolarizes the cell, thereby closing voltage-gated Ca2+ channels and limiting neuronal damage by decreasing influx of intracellular Ca2+. Unoprostone has also been shown to protect rat photoreceptors from constant light-induced damage. Lastly, unoprostone has
vasorelaxant properties, evidenced by increased choroidal blood flow and inhibition of
vasoconstrictors such as
endothelin-1. These findings indicate that a substantial clinical benefit of unoprostone is neuroprotection of RGCs.