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Functional consequences of oncogene-induced horizontal cell degeneration in the retinas of transgenic mice

Published online by Cambridge University Press:  02 June 2009

Neal S. Peachey ,
Luisa Roveri ,
Albee Messing  and
Maureen A. McCall
Neal S. Peachey
Affiliation:
Hines VA Hospital, Hines, IL & Department of Neurology, Stritch School of Medicine, Loyola University of Chicago, Maywood
Luisa Roveri
Affiliation:
Hines VA Hospital, Hines, IL & Department of Neurology, Stritch School of Medicine, Loyola University of Chicago, Maywood
Albee Messing
Affiliation:
Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison
Maureen A. McCall
Affiliation:
Waisman Center, University of Wisconsin-Madison, Madison
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Abstract

Visual function was evaluated in transgenic mice expressing the simian virus 40 early region under the control of the promoter for phenylethanolamine-N-methyltransferase. These transgenic mice undergo a degeneration of the retinal horizontal cells and the outer plexiform layer. Electroretinograms (ERGs) were recorded under stimulus conditions chosen to elicit both receptoral and postreceptoral responses. The dark-adapted a-waves obtained from transgenic mice were not different from control recordings, indicating that the degenerative process does not interfere with function of the rod photoreceptors. In comparison, the ERG b-wave was markedly reduced in transgenic mice under both dark- and light-adapted conditions. Reproducible visual evoked potentials (VEPs) were recorded from transgenic mice in response to both low luminance stimuli that isolate rod function, and to higher luminance stimuli, indicating that retinal activity is transmitted centrally to the visual cortex. However, VEPs were delayed at all stimulus luminances compared to controls. Analysis of luminance-response functions suggests that the VEP delays could reflect the combination of a decrease in synaptic efficacy and an overall loss in visual sensitivity. These functional abnormalities correlate well with the anatomical abnormalities that have been previously observed in the transgenic retina (Hammang et al., 1993), namely a reduced number of synapses between photoreceptors and second-order neurons.

Keywords

Electroretinogram (ERG)Horizontal cellsOncogeneTransgenic miceVisual evoked potential (VEP)
Type
Research Articles
Information
Visual Neuroscience , Volume 14 , Issue 4 , July 1997 , pp. 627 - 632
Copyright
Copyright © Cambridge University Press 1997

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References

Adachi-Usami, E., Ikeda, H. & Satoh, H. (1990). Halopcridol delays visually evoked cortical potentials but not electroretinograms in mice. Journal of Ocular Pharmacology 6, 203–210.CrossRefGoogle Scholar
Alexander, K.R., Fishman, G.A. & Derlacki, D.J. (1988). Mechanisms of rod-cone interaction: Evidence from congenital stationary nightblindness. Vision Research 28, 575–583.CrossRefGoogle ScholarPubMed
Alexander, K.R., Fishman, G.A., Peachey, N.S., Marchese, A.L. & Tso, M.O.M. (1992). ‘On’ response defect in paraneoplastic night blindness with cutaneous malignant melanoma. Investigative Ophthalmology and Visual Science 33, 477–483.Google ScholarPubMed
Al-Ubaidi, M.R., Hollyfield, J.G., Overbeek, P.A. & Baehr, W. (1992). Photoreceptor degeneration induced by the expression of simian virus 40 large tumor antigen in the retina of transgenic mice. Proceedings of the National Academy of Sciences of the U.S.A. 89, 1194–1198.CrossRefGoogle ScholarPubMed
Baetge, E.E., Behringer, R.R., Messing, A., Brinster, T.L. & Palmiter, R.D. (1988). Transgenic mice express the human phenylethanolamine N-methyltransferasc gene in adrenal medulla and retina. Proceedings of the National Academy of Sciences of the U.S.A. 85, 3648–3652.CrossRefGoogle ScholarPubMed
Breton, M.E., Schueller, A.W., Lamb, T.D. & Pugh, E.N. Jr. (1994). Analysis of ERG a-wave amplification and kinetics in terms of the G-protein cascade of phototransduction. Investigative Ophthalmology and Visual Science 35, 295–309.Google ScholarPubMed
Bush, R.A. & Sieving, P.A. (1994). A proximal retinal component in the primate photopic ERG a-wave. Investigative Ophthalmology and Visual Science 35, 635–645.Google ScholarPubMed
Carr, R.E., Ripps, H., Siegel, I.M. & Weale, R.A. (1966). Rhodopsin and the electrical activity of the retina in congenital night blindness. Investigative Ophthalmology 5, 497–507.Google ScholarPubMed
Falk, G. & Shiells, R.A. (1986). Do horizontal cell responses contribute to the electroretinogram (ERG) in dogfish? Journal of Physiology 381. 113P.Google Scholar
Fedderson, R.M., Ehlenfeldt, R., Yunis, W.S., Clark, H.B. & Orr, H.T. (1992). Disrupted cerebellar cortical development and progressive degeneration of Purkinje cells in SV40 T antigen transgenic mice. Neuron 9, 955–966.CrossRefGoogle Scholar
Fulton, A.B., Hansen, R.M. & Findl, O. (1995). The development of the rod photoresponse from dark-adapted rats. Investigative Ophthalmology and Visual Science 36, 1038–1045.Google ScholarPubMed
Goto, Y., Peachey, N.S., Ripps, H. & Naash, M.I. (1995). Functional abnormalities in transgenic mice expressing a mutant rhodopsin gene. Investigative Ophthalmology and Visual Science 36, 62–71.Google ScholarPubMed
Hammang, J.P., Baetge, E.E., Behringer, R.R., Brinster, R.L., Palmiter, R.D. & Messing, A. (1990). Immortalize retinal neurons derived from SV40-T-antigen-induccd tumors in transgenic mice. Neuron 4, 775–782.CrossRefGoogle ScholarPubMed
Hammang, J.P., Behringer, R.R., Baetge, E.E., Palmiter, R.D., Brinster, R.L. & Messing, A. (1993). Oncogene expression in retinal horizontal cells of transgenic mice results in a cascade of neurodegeneration. Neuron 10, 1197–1209.CrossRefGoogle Scholar
Hanahan, D. (1988). Dissecting multistep tumorigenesis in transgenic mice. Annual Review of Genetics 22. 379–387.CrossRefGoogle ScholarPubMed
Hood, D.C. & Birch, D.G. (1990). A quantitative measure of the electrical activity of human rod photoreceptors using electroretinography. Visual Neuroscience 5, 379–387.CrossRefGoogle ScholarPubMed
Hood, D.C. & Birch, D.G. (1994). Rod phototransduction in retinitis pigmentosa: Estimation and interpretation of parameters derived from the rod a-wave. Investigative Ophthalmology and Visual Science 35. 2948–2961.Google ScholarPubMed
Hood, D.C. & Birch, D.G. (1996). b wave of the scotopic (rod) electroretinogram as a measure of the activity of human on-bipolar cells. Journal of the Optical Society of America A 13, 623–633.CrossRefGoogle Scholar
Karwoski, C.J., Xu, X. & Yu, H. (1996). Current-source density analysis of the electroretinogram of the frog: Methodological issues and origin of components. Journal of the Optical Society of America A 13, 549–556.CrossRefGoogle ScholarPubMed
Masu, M., Iwakabe, H., Tagawa, Y., Miyoshi, T., Yamashita, M., Fukuda, Y., Sasaki, H., Hiroi, K., Nakamura, Y., Shigemoto, R., Takada, M., Nakamura, K., Nakao, K., Katsuki, M. & Nakanishi, S. (1995). Specific deficit of the ON response in visual transmission by targeted disruption of the mGluR6 gene. Cell 80, 757–765.CrossRefGoogle ScholarPubMed
Miller, R.F. & Dowling, J.E. (1970). Intracellular responses of the Muller (glial) cells of the mudpuppy retina: Their relation to the b-wave of the electroretinogram. Journal of Neurophysiology 33, 323–341.CrossRefGoogle Scholar
Newman, E.A. (1986). Physiological properties and possible functions of Müller cells. Neuroscience Research (Suppl.) 4. S209–S220.CrossRefGoogle ScholarPubMed
Noell, W.K. (1958). Differentiation, metabolic organization, and viability of the visual cell. Archives of Ophthalmology 60, 702–733.CrossRefGoogle ScholarPubMed
Peachey, N.S., Fishman, G.A., Derlacki, D.J. & Brigell, M.G. (1987). Psychophysical and electroretinographic findings in X-linked juvenile retinoschisis. Archives of Ophthalmology 105, 513–516.CrossRefGoogle ScholarPubMed
Peachey, N.S., Goto, Y., Al-Ubaidi, M.R. & Naash, M.I. (1993). Properties of the mouse cone-mediated electroretinogram during light adaptation. Neuroscience Letters 162, 9–11.CrossRefGoogle ScholarPubMed
Peachey, N.S., Goto, Y., Quiambao, A.B. & Al-Ubaidi, M.R. (1995). Functional consequences of oncogene-induced photoreceptor degeneration in transgenic mice. Visual Neuroscience 12, 513–522.CrossRefGoogle ScholarPubMed
Penn, R.D. & Hagins, W.A. (1969). Signal transmission along retinal rods and the origin of the electroretinographic o-wave. Nature 223. 201–205.CrossRefGoogle Scholar
Pillers, D.-A.M., Bulman, D.E., Weleber, R.G., Sigesmund, D.A., Musarella, M.A., Powell, B.R., Murphey, W.H., Westall, C., Panton, C., Becker, L.E., Worton, R.G. & Ray, P.N. (1993). Dystrophin expression in the human retina is required for normal function as defined by electroretinography. Nature Genetics 4, 82–86.CrossRefGoogle ScholarPubMed
Pillers, D.-A.M., Weleber, R.G., Woodward, W.R., Green, D.G., Chapman, V.M. & Ray, P.N. (1995). mdxCv3 mouse is a model for electroretinography of Duchenne/Becker muscular dystrophy. Investigative Ophthalmology and Visual Science 36, 462–466.Google Scholar
Ripps, H. (1982). Night blindness revisited: From man to molecules. Investigative Ophthalmology and Visual Science 23, 588–609.Google Scholar
Robson, J.G. & Frishman, L.J. (1995). Response linearity and kinetics of the cat retina: The bipolar cell component of the dark-adapted electroretinogram. Visual Neuroscience 12. 837–850.CrossRefGoogle ScholarPubMed
Robson, J.G. & Frishman, L.J. (1996). Photoreceptor and bipolar-cell contributions to the cat electroretinogram: A kinetic model for the early part of the flash response. Journal of the Optical Society of America A 13, 613–622.CrossRefGoogle Scholar
Sieving, P.A., Murayama, K. & Naarendorp, F. (1994). Push-pull model of the primate photopic electroretinogram: A role for hyperpolarizing neurons in shaping the b-wave. Visual Neuroscience 11, 519–532.CrossRefGoogle ScholarPubMed
Stockton, R.A. & Slaughter, M.M. (1989). B-wave of the electroretinogram. A reflection of ON bipolar cell activity. Journal of General Physiology 93, 101–122.CrossRefGoogle ScholarPubMed
Strain, G.M. & Tedford, B.L. (1993). Flash and pattern reversal visual evoked potentials in C57BL/6J and B6CBAF1/J mice. Brain Research Bulletin 32, 57–63.CrossRefGoogle ScholarPubMed
Tremblay, F., De Becker, I., Riddell, D.C. & Dooley, J.M. (1994). Duchenne muscular dystrophy: Negative scotopic bright-flash electroretinogram and normal dark adaptation. Canadian Journal of Ophthalmology 29, 280–283.Google ScholarPubMed
Weleber, R.G., Fillers, D.-A.M., Powell, B.R., Hanna, C.E., Magenic, R.E. & Buist, N.R.M. (1991). Aland island eye disease (Forsius-Eriksson syndrome) associated with contiguous deletion syndrome at Xp21. Archives of Ophthalmology 107, 1170–1179.CrossRefGoogle Scholar
Xu, X. & Karwoski, C.J. (1994). Current source density analysis of retinal field potentials. II. Pharmacological analysis of the b-wave and m-wave. Journal of Neurophysiology 72, 96–105.CrossRefGoogle ScholarPubMed