J Korean Ophthalmol Soc > Volume 49(7); 2008 > Article
Journal of the Korean Ophthalmological Society 2008;49(7):1146-1153.
DOI: https://doi.org/10.3341/jkos.2008.49.7.1146    Published online July 15, 2008.
N-Methyl-D-Aspartate (NMDA)-induced Apoptosis in Rabbit Retina.
Yong Wook Park, Sun Hwa Chae, Ji Woong Lee, Oh Ju Kwon, Jae Pil Shin, Chang Jin Jeon, Si Yeol Kim
1Department of Ophthalmology, Kyungpook National University, College of Medicine, Daegu, Korea. jpshin@hitel.net
2Department of Ophthalmic Optics, Busan College of Information Technology, Pusan, Korea.
3Department of Biology, Kyungpook National University, College of Natural Science, Daegu, Korea.
토끼 망막에서 NMDA에 의한 아포프토시스의 발현
박용욱1ㆍ채선화1ㆍ이지웅1ㆍ권오주2ㆍ신재필1ㆍ전창진3ㆍ김시열1
Department of Ophthalmology, Kyungpook National University, College of Medicine1, Daegu, Korea, Department of Ophthalmic Optics, Busan College of Information Technology2, Pusan, Korea, Department of Biology, Kyungpook National University, College of Natural Science3, Daegu, Korea
Correspondence:  Yong Wook Park, M.D.1
Abstract
PURPOSE
To evaluate the involvement of apoptosis in N-methyl-D-aspartate (NMDA)-induced excitotoxicity in the rabbit retina. METHODS: After intravitreal injection of 680 and 2,000 nmoles of NMDA in rabbit eyes, the eyes were enucleated at 2, 16, and 60 hours and 1 and 2 weeks. The apoptotic cell death was determined with TdT-mediated biotin-dUTP nick end labeling (TUNEL) stain, and immunohistochemical stains of Bcl-2, Bax, and caspase-3 were performed. RESULTS: TUNEL showed increased labeling scattered in the ganglion cell layer and inner nuclear layer from 16 to 60 hours. The number of TUNEL-positive nuclei decreased at 60 hours, and none was observed at 2 hours, 1 week, and 2 weeks. More TUNEL-positive nuclei were seen with injection of 2,000 nmoles compared to 680 nmoles. Bcl-2, Bax, and caspase-3 were seen histologically as early as 2 hours in the ganglion cell layer and inner nuclear layer; there was no stained nuclei with the TUNEL stain. At 2 hours after intravitreal NMDA injection, Bcl-2, Bax, and caspase-3 were also stained in Muller cells. CONCLUSIONS: This study showed that apoptosis is involved in NMDA-induced excitotoxicity in the rabbit retina. Bcl-2, Bax, and caspase-3 may play important roles in modulating the apoptosis in NMDA-induced excitotoxicity, and Muller cells are involved in the apoptotic pathway.
Key Words: Apoptosis;Bax;Bcl-2;Caspase-3;NMDA
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