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Morphological and functional evaluation of an animal model for the retinal degeneration induced by N-methyl-N-nitrosourea  

Jeong, Eo-Jin (Department of Anatomy, Catholic Institute for Advanced Biomaterials, The Catholic University of Korea College of Medicine)
Paik, Sun-Sook (Department of Anatomy, Catholic Institute for Advanced Biomaterials, The Catholic University of Korea College of Medicine)
Jung, Sung-Won (Department of Anatomy, Catholic Institute for Advanced Biomaterials, The Catholic University of Korea College of Medicine)
Chun, Myung-Hoon (Department of Anatomy, Catholic Institute for Advanced Biomaterials, The Catholic University of Korea College of Medicine)
Kim In-Beom (Department of Anatomy, Catholic Institute for Advanced Biomaterials, The Catholic University of Korea College of Medicine)
Publication Information
Anatomy and Cell Biology / v.44, no.4, 2011 , pp. 314-323 More about this Journal
Abstract
The retinal degeneration (RD) is a general cause of blindness. To study its pathophysiology and evaluate the eff ects of new therapeutic agents before clinical trials, it is essential to establish reliable and stable animal models. This study evaluated a RD animal model in which blindness was induced by N-methyl-N-nitrosourea (MNU), a potent retinotoxin leading to apoptosis of photoreceptors. MNU was applied to the Sprague-Dawley rats by a single intraperitoneal injection in different doses (40, 50, and 60 mg/kg). Th e retinal functions were examined at 1 week after MNU injection by electroretinogram (ERG). Afterwards, each retina was examined by hematoxylin and eosin stain and immunohistochemistry with anti-glial fibrillary acidic protein antibody. Upon MNU injection of 40, 50 and 60 mg/kg, the ERG amplitude of a-waves showed significant reductions of 7, 26, and 44%, respectively, when compared to that of normal a-waves. The b-wave amplitudes were about 89, 65, and 58% of normal b-waves in the response to scotopic light stimulus. At 1 week, 2 weeks, and 4 weeks aft er MNU injection (50 mg/kg), all scotopic ERG components decreased progressively. In addition, degeneration of retinal neurons was observed in a time- and dose-dependent manner after MNU injection. Taken together, functional reduction following RD induced by MNU correlates with morphological changes. Thus, this RD rat model may be a useful model to study its pathophysiology and to evaluate the effects of new therapeutic agents before clinical trials.
Keywords
Animal models; Electroretinography; N-methyl-N-nitrosourea; Retinal degeneration;
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