Latanoprost exerts neuroprotective activity in vitro and in vivo.

Abstract Prostaglandins may influence cyclo-oxygenase (COX-2) and nitric oxide (NO) synthase activity, thus interfering with ischemia-induced neurotoxic processes. The prostaglandin synthetic derivative, latanoprost was tested in different in vivo and in vitro models of neuronal damage in order to study its influence on these processes. Ischemia was induced in rats by bilateral occlusion of the carotid arteries for 30 min. Latanoprost (0.01 mg kg −1 per die, i.p. for 3 days) or the ionotropic glutamate receptors antagonist, MK-801 (0.1 mg kg −1 per die, i.p. for 3 days) were equal in preventing lactate accumulation in retinal tissue of animals subjected to acute ischemia. Similar results were obtained in animals with retinal ischemia induced by increasing intraocular pressure to 120 mm Hg for 45 min. PGF 2α  , PGE 2  , latanoprost and acid of latanoprost (PhXA85) reduced the release of LDH from primary cultures of human retinal cells in vitro subjected to glutamate (10  μ M ) or hypoxia/re-oxygenation exposure. This effect was observed only at concentrations of 1–0.01  μ M for PGF 2α and PGE 2 , and of 0.1–0.001  μ M for latanoprost (0.01  μ M –0.1 n M for PhXA85). The COX-2 activity in cultured retinal cells exposed to glutamate was measured as PGE 2 production when latanoprost was applied compared to arachidonic acid (AA) at different molar concentrations. The COX-2 activity was reduced by arachidonic acid (0.1–0.01  μ M ) as well as by latanoprost (0.1–0.001  μ M ) and PhXA85 (0.01–0.001  μ M ) in retinal cells exposed to glutamate. Inhibition of inducible NO synthase was also found with the same drug concentrations. These results suggest that latanoprost exerts a neuroprotective activity in vitro and in vivo. This effect seems to be present only at low concentrations of the drug. A negative feedback on neuronal COX-2 activity may be possibly involved.