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Exp Neurobiol 2019; 28(1): 62-73
Published online February 19, 2019
https://doi.org/10.5607/en.2019.28.1.62
© The Korean Society for Brain and Neural Sciences
So Min Ahn1, Jungryul Ahn2, Seongkwang Cha2, Cheolmin Yun1, Tae Kwann Park3, Yong Sook Goo2*, and Seong-Woo Kim1*
1Department of Ophthalmology, Korea University College of Medicine, Seoul 08373, Korea.
2Department of Physiology, Chungbuk National University School of Medicine, Cheongju 28644, Korea.
3Department of Ophthalmology, Soonchunhyang University Hospital Bucheon, Bucheon 14584, Korea.
Correspondence to: *To whom correspondence should be addressed.
Yong Sook Goo, TEL: 82-43-261-2870, FAX: 82-43-272-1603
e-mail: ysgoo@chungbuk.ac.kr
Seong-Woo Kim, TEL: 82-2-2626-1260, FAX: 82-2-857-8580
e-mail: ksw64723@korea.ac.kr
Since genetic models for retinal degeneration (RD) in animals larger than rodents have not been firmly established to date, we sought in the present study to develop a new rabbit model of drug-induced RD. First, intravitreal injection of N-methyl-N-nitrosourea (MNU) without vitrectomy in rabbits was performed with different doses. One month after injection, morphological changes in the retinas were identified with ultra-wide-field color fundus photography (FP) and fundus autofluorescence (AF) imaging as well as spectral-domain optical coherence tomography (OCT). Notably, the degree of RD was not consistently correlated with MNU dose. Then, to check the effects of vitrectomy on MNU-induced RD, the intravitreal injection of MNU after vitrectomy in rabbits was also performed with different doses. In OCT, while there were no significant changes in the retinas for injections up to 0.1 mg (i.e., sham, 0.05 mg, and 0.1 mg), outer retinal atrophy and retinal atrophy of the whole layer were observed with MNU injections of 0.3 mg and 0.5 mg, respectively. With this outcome, 0.2 mg MNU was chosen to be injected into rabbit eyes (n=10) at two weeks after vitrectomy for further study. Six weeks after injection, morphological identification with FP, AF, OCT, and histology clearly showed localized outer RD - clearly bordered non-degenerated and degenerated outer retinal area - in all rabbits. We suggest our post-vitrectomy MNU-induced RD rabbit model could be used as an interim animal model for visual prosthetics before the transition to larger animal models.
Keywords: Retinal degeneration, Intravitreal injection, N-methyl-N-nitrosourea, Vitrectomy, Optical coherence tomography, Animal model