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Originally published In Press as doi:10.1167/iovs.08-2863 on December 13, 2008
 (Investigative Ophthalmology and Visual Science. 2009;50:1371-1377.)
© 2009 by The Association for Research in Vision and Ophthalmology, Inc.
doi:10.1167/iovs.08-2863
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Generation of a Transgenic Rabbit Model of Retinal Degeneration

Mineo Kondo,1 Takao Sakai,1 Keiichi Komeima,1 Yukihide Kurimoto,1 Shinji Ueno,1 Yuji Nishizawa,2 Jiro Usukura,3 Takashi Fujikado,4 Yasuo Tano,5 and Hiroko Terasaki1

1From the Department of Ophthalmology, Graduate School of Medicine, and the 3Department of Materials Physics and Engineering, Graduate School of Engineering, Nagoya University, Nagoya, Japan; the 2Research Institute of Life and Health Sciences, Chubu University, Kasugai, Japan; and the 4Departments of Applied Visual Science and 5Ophthalmology, Graduate School of Medicine, Osaka University, Suita, Japan.

PURPOSE. To generate a transgenic (Tg) rabbit model of retinal degeneration and to characterize the pattern of degeneration by using histology and electrophysiology.

METHODS. Rhodopsin Pro347Leu Tg rabbits were generated by BAC transgenesis. Tg rabbits were identified by Southern blot analysis, and the expression levels were measured by quantitative RT-PCR. Retinal histology was examined by light and electron microscopy and immunohistochemistry. Retinal function was assessed by full-field electroretinograms (ERGs).

RESULTS. Six lines of Tg rabbits were generated, and two lines with higher levels of expression showed rod-dominant progressive retinal degeneration. Retinal histology indicated a marked regional variation in the loss of photoreceptors with the central retina more severely affected than the peripheral retina. The characteristics of the ERGs of transgenic rabbits indicated that the rod components of the ERGs were reduced to only 5% by 48 weeks, whereas the cone components remained at 35% in the wild-type at the same time point. The retinal ultrastructure of Tg rabbits showed a large number of small vesicles that accumulated in the extracellular space of the photoreceptors.

CONCLUSIONS. To the best of the authors’ knowledge, this is the first rabbit model of progressive retinal degeneration. Because rabbits have large eyes and are easy to handle and breed, they will provide a useful animal model for the study of the pathophysiology of and new treatments for retinal degeneration.




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T. Sakai, M. Kondo, S. Ueno, T. Koyasu, K. Komeima, and H. Terasaki
Supernormal ERG Oscillatory Potentials in Transgenic Rabbit with Rhodopsin P347L Mutation and Retinal Degeneration
Invest. Ophthalmol. Vis. Sci., September 1, 2009; 50(9): 4402 - 4409.
[Abstract] [Full Text] [PDF]


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