Latanoprost exerts neuroprotective activity in vitro and in vivo

Prostaglandins may influence cyclo-oxygenase (COX-2) and nitric oxide (NO) synthase activity, thus interfering with ischemia-induced neurotoxic proces ses. The prostaglandin synthetic derivative, latanoprost was tested in diff erent 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 occ lusion 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 lacta te accumulation in retinal tissue of animals subjected to acute ischemia. S imilar results were obtained in animals with retinal ischemia induced by in creasing intraocular pressure to 120 mm Hg for 45 min. PGF(2 alpha), PGE(2) , latanoprost and acid of latanoprost (PhXA85) reduced the release of LDH f rom primary cultures of human retinal cells in vitro subjected to glutamate (10 muM) or hypoxia/re-oxygenation exposure. This effect was observed only at concentrations of 1-0.01 muM for PGF(2 alpha) and PGE(2), and of 0.1-0. 001 muM for latanoprost (0.01 muM-0.1 nM for PhXA85). The COX-2 activity in cultured retinal cells exposed to glutamate was measured as PGE(2) product ion when latanoprost was applied compared to arachidonic acid (AA) at diffe rent molar concentrations. The COX-2 activity was reduced by arachidonic ac id (0.1-0.01 muM) as well as by latanoprost (0.1-0.001 muM) and PhXA85 (0.0 1-0.001 muM) in retinal cells exposed to glutamate. Inhibition of inducible NO synthase was also found with the same drug concentrations. These result s suggest that latanoprost exerts a neuroprotective activity in vitro and i n vivo. This effect seems to be present only at low concentrations of the d rug. A negative feed back on neuronal COX-2 activity may be possibly involv ed, (C) 2001 Academic Press.