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Evaluation of visual function in Royal College of Surgeon rats using a depth perception visual cliff test

Published online by Cambridge University Press:  31 January 2019

Adi Tzameret ,
Ifat Sher ,
Victoria Edelstain ,
Michael Belkin ,
Ofra Kalter-Leibovici ,
Arieh S. Solomon  and
Ygal Rotenstreich
Adi Tzameret
Affiliation:
Goldschleger Eye Research Institute, Sheba Medical Center, Tel HaShomer, Israel Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Ifat Sher
Affiliation:
Goldschleger Eye Institute, Sheba Medical Center, Tel HaShomer, Israel
Victoria Edelstain
Affiliation:
Goldschleger Eye Institute, Sheba Medical Center, Tel HaShomer, Israel Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Michael Belkin
Affiliation:
Goldschleger Eye Research Institute, Sheba Medical Center, Tel HaShomer, Israel Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Ofra Kalter-Leibovici
Affiliation:
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel Unit of Cardiovascular Epidemiology, Gertner Institute for Epidemiology and Health Policy Research, Ramat Gan, Israel
Arieh S. Solomon*
Affiliation:
Goldschleger Eye Research Institute, Sheba Medical Center, Tel HaShomer, Israel Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Ygal Rotenstreich*
Affiliation:
Goldschleger Eye Institute, Sheba Medical Center, Tel HaShomer, Israel Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
*
*Address correspondence to: Ygal Rotenstreich, Email:[email protected]; Arieh Solomon, Email:[email protected]
*Address correspondence to: Ygal Rotenstreich, Email:[email protected]; Arieh Solomon, Email:[email protected]
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Abstract

Preserving of vision is the main goal in vision research. The presented research evaluates the preservation of visual function in Royal College of Surgeon (RCS) rats using a depth perception test. Rats were placed on a stage with one side containing an illusory steep drop (“cliff”) and another side with a minimal drop (“table”). Latency of stage dismounting and the percentage of rats that set their first foot on the “cliff” side were determined. Nondystrophic Long–Evans (LE) rats were tested as control. Electroretinogram and histology analysis were used to determine retinal function and structure. Four-week-old RCS rats presented a significantly shorter mean latency to dismount the stage compared with 6-week-old rats (mean ± standard error, 13.7 ± 1.68 vs. 20.85 ± 6.5 s, P = 0.018). Longer latencies were recorded as rats aged, reaching 45.72 s in 15-week-old rats (P < 0.00001 compared with 4-week-old rats). All rats at the age of 4 weeks placed their first foot on the table side. By contrast, at the age of 8 weeks, 28.6% rats dismounted on the cliff side and at the age of 10 and 15 weeks, rats randomly dismounted the stage to either table or cliff side. LE rats dismounted the stage faster than 4-week-old RCS rats, but the difference was not statistically significant (7 ± 1.58 s, P = 0.057) and all LE rats dismounted on the table side. The latency to dismount the stage in RCS rats correlated with maximal electroretinogram b-wave under dark and light adaptation (Spearman’s rho test = −0.603 and −0.534, respectively, all P < 0.0001), outer nuclear layer thickness (Spearman’s rho test = −0.764, P = 0.002), and number of S- and M-cones (Spearman’s rho test = −0.763 [P = 0.002], and −0.733 [P = 0.004], respectively). The cliff avoidance test is an objective, quick, and readily available method for the determination of RCS rats’ visual function.

Keywords

Retinal degenerationVisual functionRCS ratsERG
Type
Research Article
Information
Visual Neuroscience , Volume 36 , 2019 , E002
Copyright
Copyright © Cambridge University Press 2019 

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Footnotes

†

These authors contributed equally.

References

Bourne, M.C., Campbell, D.A. & Tansley, K. (1938). Hereditary degeneration of the rat retina. British Journal of Ophthalmology 22, 613–623.CrossRefGoogle ScholarPubMed
Bush, R.A., Hawks, K.W. & Sieving, P.A. (1995). Preservation of inner retinal responses in the aged Royal College of Surgeons rat. Evidence against glutamate excitotoxicity in photoreceptor degeneration. Investigative Ophthalmology & Visual Science 36, 2054–2062.Google ScholarPubMed
Cumming, B. & DeAngelis, G. (2001). The physiology of stereopsis. Annual Review of Neuroscience 24, 203–238.CrossRefGoogle ScholarPubMed
D’Cruz, P.M., Yasumura, D., Weir, J., Matthes, M.T., Abderrahim, H., LaVail, M.M. & Vollrath, D. (2000). Mutation of the receptor tyrosine kinase gene Mertk in the retinal dystrophic RCS rat. Human Molecular Genetics 9, 645–651.CrossRefGoogle ScholarPubMed
DiLoreto, D., del Cerro, M., Reddy, S.V., Janardhan, S., Cox, C., Wyatt, J. & Balkema, G.W. (1996). Water escape performance of adult RCS dystrophic and congenic rats: A functional and histomorphometric study. Brain Research 717, 165–172.CrossRefGoogle ScholarPubMed
Edwards, R.B. & Szamier, R.B. (1977). Defective phagocytosis of isolated rod outer segments by RCS rat retinal pigment epithelium in culture. Science 197, 1001–1003.CrossRefGoogle ScholarPubMed
Gal, A., Li, Y., Thompson, D.A., Weir, J., Orth, U., Jacobson, S.G., Apfelstedt-Sylla, E. & Vollrath, D. (2000). Mutations in MERTK, the human orthologue of the RCS rat retinal dystrophy gene, cause retinitis pigmentosa. Nature Genetics 26, 270–271.CrossRefGoogle ScholarPubMed
Gamm, D.M., Wang, S., Lu, B., Girman, S., Holmes, T., Bischoff, N., Shearer, R.L., Sauve, Y., Capowski, E., Svendsen, C.N. & Lund, R.D. (2007). Protection of visual functions by human neural progenitors in a rat model of retinal disease. PloS One 2, e338.CrossRefGoogle Scholar
Girman, S., Wang, S. & Lund, R. (2005). Time course of deterioration of rod and cone function in RCS rat and the effects of subretinal cell grafting: A light-and dark-adaptation study. Vision Research 45, 343–354.CrossRefGoogle ScholarPubMed
Glynn, D., Bortnick, R.A. & Morton, A.J. (2003). Complexin II is essential for normal neurological function in mice. Human Molecular Genetics 12, 2431–2448.CrossRefGoogle ScholarPubMed
Haamedi, N., Stevanato, L., Carter, D., Brooke, G., Young, M., Coffey, P., Sinden, J., Patel, S. & Vugler, A. (2016). Efficacy and safety of human retinal progenitor cells, Translational Vision Science & Technology 5, 6.Google Scholar
Hartong, D.T., Berson, E.L. & Dryja, T.P. (2006). Retinitis pigmentosa. Lancet 368, 1795–1809.CrossRefGoogle ScholarPubMed
Herron, W.L., Riegel, B.W., Myers, O.E. & Rubin, M.L. (1969). Retinal dystrophy in the rat-a pigment epithelial disease. Investigative Ophthalmology & Visual Science 8, 595–604.Google ScholarPubMed
Hou, B., Fu, Y., Weng, C., Liu, W., Zhao, C. & Yin, Z.Q. (2017). Homeostatic plasticity mediated by rod-cone gap junction coupling in retinal degenerative dystrophic RCS rats. Frontiers in Cellular Neuroscience 11, 98.CrossRefGoogle ScholarPubMed
Huang, Y.M., Yin, Z.Q., Liu, K. & Huo, S.J. (2011). Temporal and spatial characteristics of cone degeneration in RCS rats. Japanese Journal of Ophthalmology 55, 155–162.CrossRefGoogle ScholarPubMed
Kofuji, P., Ceelen, P., Zahs, K.R., Surbeck, L.W., Lester, H.A. & Newman, E.A. (2000). Genetic inactivation of an inwardly rectifying potassium channel (Kir4.1 subunit) in mice: Phenotypic impact in retina. Journal of Neuroscience 20, 5733–5740.CrossRefGoogle ScholarPubMed
Little, C.W., Cox, C., Wyatt, J., del Cerro, C. & del Cerro, M. (1998). Correlates of photoreceptor rescue by transplantation of human fetal RPE in the RCS rat. Experimental Neurology 149, 151–160.CrossRefGoogle ScholarPubMed
Lu, B., Malcuit, C., Wang, S., Girman, S., Francis, P., Lemieux, L., Lanza, R. & Lund, R. (2009). Long-term safety and function of RPE from human embryonic stem cells in preclinical models of macular degeneration. Stem Cells 27, 2126–2135.CrossRefGoogle ScholarPubMed
Machida, S., Raz-Prag, D., Fariss, R.N., Sieving, P.A. & Bush, R.A. (2008). Photopic ERG negative response from amacrine cell signaling in RCS rat retinal degeneration. Investigative Ophthalmology & Visual Science 49, 442–452.CrossRefGoogle ScholarPubMed
Matthes, M.T. & LaVail, M.M. (1989). Inherited retinal dystrophy in the RCS rat: Composition of the outer segment debris zone. Progress in Clinical & Biological Research 314, 315–330.Google ScholarPubMed
McGill, T.J., Bohana-Kashtan, O., Stoddard, J.W., Andrews, M.D., Pandit, N., Rosenberg-Belmaker, L.R., Wiser, O., Matzrafi, L., Banin, E. & Reubinoff, B. (2017). Long-term efficacy of GMP grade xeno-free hESC-derived RPE cells following transplantation. Translational Vision Science & Technology 6, 17.CrossRefGoogle ScholarPubMed
McGill, T.J., Douglas, R.M., Lund, R.D. & Prusky, G.T. (2004). Quantification of spatial vision in the royal College of Surgeons rat. Investigative Ophthalmology & Visual Science 45, 932–936.CrossRefGoogle ScholarPubMed
McGill, T.J., Lund, R.D., Douglas, R.M., Wang, S., Lu, B., Silver, B.D., Secretan, M.R., Arthur, J.N. & Prusky, G.T. (2007). Syngeneic Schwann cell transplantation preserves vision in RCS rat without immunosuppression. Investigative Ophthalmology & Visual Science 48, 1906–1912.CrossRefGoogle ScholarPubMed
McGill, T.J., Prusky, G.T., Douglas, R.M., Yasumura, D., Matthes, M.T., Lowe, R.J., Duncan, J.L., Yang, H., Ahern, K., Daniello, K.M., Silver, B. & LaVail, M.M. (2012). Discordant anatomical, electrophysiological, and visual behavioral profiles of retinal degeneration in rat models of retinal degenerative disease, Investigative Opthalmology & Visual Science 53, 6232.CrossRefGoogle ScholarPubMed
Penn, R.D. & Hagins, W.A. (1969). Signal transmission along retinal rods and the origin of the electroretinographic a-wave. Nature 223, 201–204.CrossRefGoogle ScholarPubMed
Perlman, I. (1978). Dark-adaptation in abnormal (RCS) rats studied electroretinographically. Journal of Physiology 278, 161–175.CrossRefGoogle ScholarPubMed
Russell, J. & Lashley, K. (1934). The mechanism of vision: XI. A preliminary test of innate organization. The Journal of Genetic Psychology 45, 136–144.Google Scholar
Sauve, Y., Lu, B. & Lund, R. (2004). The relationship between full field electroretinogram and perimetry-like visual thresholds in RCS rats during photoreceptor degeneration and rescue by cell transplants. Vision Research 44, 9–18.CrossRefGoogle ScholarPubMed
Thomas, B.B., Seiler, M.J., Sadda, S.R., Coffey, P.J. & Aramant, R.B. (2004). Optokinetic test to evaluate visual acuity of each eye independently. Journal of Neuroscience Methods 138, 7–13.CrossRefGoogle ScholarPubMed
Trejo, L.J. & Cicerone, C.M. (1982). Retinal sensitivity measured by the pupillary light reflex in RCS and albino rats. Vision Research 22, 1163–1171.CrossRefGoogle ScholarPubMed
Tzameret, A., Sher, I., Belkin, M., Treves, A.J., Meir, A., Nagler, A., Levkovitch-Verbin, H., Barshack, I., Rosner, M. & Rotenstreich, Y. (2014). Transplantation of human bone marrow mesenchymal stem cells as a thin subretinal layer ameliorates retinal degeneration in a rat model of retinal dystrophy. Experimental Eye Research 118, 135–144.CrossRefGoogle Scholar
Tzameret, A., Sher, I., Belkin, M., Treves, A.J., Meir, A., Nagler, A., Levkovitch-Verbin, H., Rotenstreich, Y. & Solomon, A.S. (2015). Epiretinal transplantation of human bone marrow mesenchymal stem cells rescues retinal and vision function in a rat model of retinal degeneration. Stem Cell Research 15, 387–394.CrossRefGoogle Scholar
Walk, R., Gibson, E.J. & Tighe, T. (1957). Behavior of light-and dark-reared rats on a visual cliff. Science 126, 80–81.CrossRefGoogle ScholarPubMed
Wurziger, K., Lichtenberger, T. & Hanitzsch, R. (2001). On-bipolar cells and depolarising third-order neurons as the origin of the ERG-b-wave in the RCS rat. Vision Research 41, 1091–1101.CrossRefGoogle ScholarPubMed
Young, B., Eggenberger, E. & Kaufman, D. (2012). Current electrophysiology in ophthalmology: A review. Current Opinion in Ophthalmology 23, 497–505.CrossRefGoogle ScholarPubMed
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