Latanoprost has neuroprotective ability in an intraocular pressure–independent way in vitro and in vivo.

Abstract

Abstract: : Purpose: Latanoprost, a prostaglandin F2α(PGF2α) analogue, not only has a powerful ocular hypotensive property but also is suggested to have a potential neuroprotective ability. Retinal neurons and glia are known to have PGF receptors. The purpose of this study is to test whether latanoprost exerts the anti–apoptotic ability on retinal neurons and glia in an intraocular pressure (IOP)–independent fashion in vitro and in vivo. Methods: : R28 cells, a model of retinal neurons, were serum–deprived for 24 hours to undergo apoptosis. Varying concentrations of latanoprost acid or vehicle were added with or without inhibitors for phosphatidylinositol 3 kinase (PI3K), mitogen activated protein kinase (MAPK), protein kinase C(PKC) , or cyclic GMP (cGMP). The cells were immunostained against activated caspase 3 and counterstained with Hoechst dye. Male Sprague–Dawley rats were made diabetic by intravenous injection of streptozotocin (STZ). After 1month, latanoprost was instilled on unilateral eyes and balanced saline solution (BSS) on contralateral eyes once daily for 5 days. Whole mount retinas were subjected to terminal d–UTP nick end labeling (TUNEL). Results: Latanoprost acid rescued R28 cells from apoptosis in a dose–dependent fashion with an optimal concentration of 1µM (P<0.01) . PKC and MAPK, but not cGMP, inhibitors antagonized this effect. Diabetic retinas treated with latanoprost had less TUNEL positive cells (12.8±5.3/0.5cm² ) than those treated with BSS (50.9±21.2/0.5 cm²) (P<0.05). IOP was not different between the eyes. Conclusions:Latanoprost is neuroprotective in an IOP–independent manner.

Keywords: apoptosis/cell death • diabetic retinopathy • neuroprotection