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Morphological alterations in retinal neurons in the S334ter-line3 transgenic rat

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Abstract

The S334ter-line-3 rat is a transgenic model of retinal degeneration developed to express a rhodopsin mutation similar to that found in human retinitis pigmentosa (RP) patients. Previous studies have focused on physiological changes in retinal cells and higher centers of the visual system with this model of retinal degeneration. However, little is known about the morphological changes in retinal cells during the development of the S334ter-line-3 rat. In order to understand and aid vision-rescue strategies, our aim has been to describe the retinal degeneration pattern in this model. We focus on changes in the morphologies of horizontal, bipolar, and amacrine cells in developing S334ter-line-3 rat retinas. Degeneration of photoreceptors begins in the central retina and progresses toward the periphery. In retinas at post-natal day 15 (P15), horizontal and rod bipolar cells show normal morphology. However, at P21, horizontal and rod bipolar cells exhibit abnormal processes at the outer plexiform layer, whereas the outer nuclear layer is significantly thinner. A glial reaction occurs concomitantly. In contrast, modifications in cone-bipolar and amacrine cells are much slower and do not occur until P90 and P180, respectively. The density of horizontal and rod-bipolar cells significantly drops after P60. Overall, the S334ter-line-3 model exhibits the hallmarks of cellular remodeling caused by photoreceptor degeneration. Its moderately fast time course makes the S334ter-line-3 a good model for studying vision-rescue strategies.

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Acknowledgements

We thank Dr. Mathew LaVail for providing the transgenic homozygous animals. We also thank Xiwu Cao and Jun-Kwan Lee for their comments and Denise Steiner for administrative assistance.

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Authors and Affiliations

  1. Department of Biomedical Engineering and Center for Vision Science and Technology, University of Southern California, Denney Research Building 140, Los Angeles, CA, 90089-1111, USA

    Aditi Ray, Leanne Chan, Norberto M. Grzywacz, James Weiland & Eun-Jin Lee

  2. Department of Biology, University of Southern California, Denney Research Building 140, Los Angeles, CA, 90089-1111, USA

    Gerald J. Sun

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  1. Aditi Ray
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  2. Gerald J. Sun
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  3. Leanne Chan
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  4. Norberto M. Grzywacz
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  6. Eun-Jin Lee
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Correspondence to Eun-Jin Lee.

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This work was supported by a Women in Science and Engineering Research Grant and a James H. Zumberge Research Grant to E.-J.L., National Eye Institute Grants EY08921 and EY11170 to N.M.G., and National Eye Institute Grant EY03040 and National Science Foundation Grant EEC 0310723 to J.D.W., D.R.H., and M.S.H.

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Ray, A., Sun, G.J., Chan, L. et al. Morphological alterations in retinal neurons in the S334ter-line3 transgenic rat. Cell Tissue Res 339, 481–491 (2010). https://doi.org/10.1007/s00441-009-0916-5

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