title: Beneficial protective effect of pramipexole on light-induced retinal damage in mice.
abstract: We investigated the effects of pramipexole, a potent dopamine receptor D2/D3 agonist, on light-induced retinal damage in mice, H2O2-induced retinal pigment epithelium ARPE-19 cell injury in humans, and hydroxyl radical scavenging activity in a cell-free system. Pramipexole (0.1 and 1 mg/kg body weight) was orally administered to mice 1 h before light exposure (5000 lux, 2 h). Electrophysiological and morphologic studies were performed to evaluate the effects of the pramipexole on light-induced retinal damage in mice. Pramipexole significantly prevented the reduction of the a- and b-wave electroretinogram (ERG) amplitudes caused by light exposure in a dose-dependent manner. In parallel, damage to the inner and outer segments (IS/OS) of the photoreceptors, loss of photoreceptor nuclei, and the number of Tdt-mediated dUTP nick-end labeling (TUNEL)-positive cells in the outer nuclear layer (ONL) caused by light exposure were notably ameliorated by pramipexole. Additionally, pramipexole suppressed H2O2-induced ARPE-19 cell death in vitro in a concentration-dependent manner. The effect of pramipexole was significant at concentrations of 10(-6) M or higher. Pramipexole also significantly prevented H2O2-induced activation of caspases-3/7 and the intracellular accumulation of reactive oxygen species (ROS) in a concentration-dependent manner ranging from 10(-5) to 10(-3) M. Furthermore, pramipexole increased the scavenging activity toward a hydroxyl radical generated from H2O2 in a Fenton reaction. Our results suggest that pramipexole protects against light-induced retinal damage as an antioxidant and that it may be a novel and effective therapy for retinal degenerative disorders, such as dry age-related macular degeneration.
authors.affiliation: Research and Development Division, Santen Pharmaceutical Co., Ltd., 4-20, Ofuka-cho, Kita-ku, Osaka 530-8552, Japan; Graduate School of Biological Sciences, Nara Institute of Science and Technology, 8916-5 Takayama-cho, Ikoma-shi, Nara 630-0192, Japan. Electronic address: keiichi.shibagaki@santen.co.jp.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Shibagaki
authors.affiliation: Corporate Development Division, Santen Pharmaceutical Co., Ltd., 4-20, Ofuka-cho, Kita-ku, Osaka 530-8552, Japan.
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Okamoto
authors.affiliation: Research and Development Division, Santen Pharmaceutical Co., Ltd., 4-20, Ofuka-cho, Kita-ku, Osaka 530-8552, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Katsuta
authors.affiliation: Research and Development Division, Santen Pharmaceutical Co., Ltd., 4-20, Ofuka-cho, Kita-ku, Osaka 530-8552, Japan.
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Nakamura
mesh_terms: D000818:Animals; D017209:Apoptosis; D052160:Benzothiazoles / Q000494:pharmacology*; D016923:Cell Death; D004195:Disease Models, Animal; D004596:Electroretinography; D020287:In Situ Nick-End Labeling; D008027:Light / Q000009:adverse effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D020419:Photoreceptor Cells, Vertebrate / Q000187:drug effects / Q000473:pathology*; D000077487:Pramipexole; D012162:Retinal Degeneration / Q000209:etiology / Q000235:genetics* / Q000473:pathology
chemical_list: D052160:Benzothiazoles; D000077487:Pramipexole
keywords: Age-related macular degeneration; Antioxidant; Apoptosis; Light-induced retinal damage; Pramipexole