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Alterations of Müller (glial) cells in dystrophic retinae of RCS rats

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Journal of Neurocytology

Summary

We have carried out a light microscopical study of Müller cells in the retinae of rats with inherited retinal dystrophy (Royal College of Surgeons rats). Isolated retinae of both control and Royal College of Surgeons rats were exposed to a Procion Yellow solution which is taken up selectively into Müller cells. The shape of the cells was then studied by confocal microscopy. Enzymatically isolated Müller cells were studied immunocytochemically with antibodies against glial fibrillary acidic protein, cathepsin D, β-amyloid precursor protein, bcl-2 protooncogene product, and glutamine synthetase. Müller cells from RCS retinae were shorter than those from control retinae, and showed a coarse hypertrophy of their distal (sclerad) processes. In Müller cells isolated from the retinae of Royal College of Surgeon's rats, the expression of glial fibrilliary acidic protein, cathepsin D, β-amyloid precursor protein and bcl-2 protooncogene product was increased, and the expression of glutamine synthetase was reduced. Obviously, loss of neighbouring neurons leads to major alterations of both the shape and metabolism of Müller cells. The expression of enzymes that serve functional glio-neuronal interactions, such as glutamine synthetase, seems to be down-regulated, whereas proteins involved in cell reconstruction (cathepsin D), cell repair (possibly β-amyloid precursor protein), and protection against apoptotic cell death (bcl-2 protooncogene product), are up-regulated, together with the ‘pathological marker’ glial fibrilliary acidic protein.

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References

  • Ashall, F. &Goate, A. M. (1994) Role of the β-amyloid precursor protein in Alzheimer's disease.Trends in Biochemical Sciences 19, 42–6.

    PubMed  Google Scholar 

  • Bernstein, H.-G., Reichenbach, A., Kirschke, H. &Wiederanders, B. (1989) Cell type-specific distribution of cathepsin B and D immunoreactivity within the rabbit retina.Neuroscience Letters 98, 135–8.

    PubMed  Google Scholar 

  • Bignami, A. &Dahl, D. (1979) The radial glia of Müller in the rat retina and their response to injury. An immunofluorescence study with antibodies to the glial fibrillary acidic (GFA) protein.Experimental Eye Research 28, 63–9.

    PubMed  Google Scholar 

  • Björklund, H., Bignami, A. &Dahl, D. (1985) Immunohistochemical demonstration of glial fibrillary acidic protein in normal rat Müller glia and retinal astrocytes.Neuroscience Letters 54, 363–8.

    PubMed  Google Scholar 

  • Bok, D. &Hall, M. O. (1971) The role of the pigment epithelium in the etiology of inherited retinal dystrophy in the rat.Journal of Cell Biology 49, 664–82.

    PubMed  Google Scholar 

  • Bourne, M. C., Campbell, D. A. &Tansley, K. (1938) Hereditary degeneration of the rat retina.British Journal of Ophthalmology 22, 613–23.

    Google Scholar 

  • Burden, E. M., Yates, C. M., Reading, H. W., Bitensky, L. &Chayen, J. (1971) Investigation into the structural integrity of lysosomes in the normal and dystrophic rat retina.Experimental Eye Research 12, 159–65.

    PubMed  Google Scholar 

  • Buxbaum, J. D., Oishi, M., Chen, H. I., Pinkas-Kramarski, R., Jaffe, E. A., Gandy, S. E. &Greengard, P. (1992) Cholinergic agonists and interleukin 1 regulate processing and secretion of the Alzheimer β/A4 amyloid protein precursor.Proceedings of the National Academy of Sciences (USA) 89, 10075–8.

    Google Scholar 

  • Caldwell, R. B., Roque, R. S. &Solomon, S. W. (1989) Increased vascular density and vitreo-retinal membranes accompany vascularization of the pigment epithelium in the dystrophic rat retina.Current Eye Research 8, 923–37.

    PubMed  Google Scholar 

  • Caley, D. W., Johnson, C. &Liebelt, R. A. (1972) The postnatal development of the retina in the normal and rodless CBA mouse: a light and electron microscopic study.American Journal of Anatomy 133, 179–212.

    PubMed  Google Scholar 

  • Chen, S. T., Garey, L. J. &Jen, L. S. (1994a) Bcl-2 protooncogene protein immunoreactivity in normally developing and axotomised rat retinas.Neuroscience Letters 172, 11–14.

    PubMed  Google Scholar 

  • Chen, S. T., Wang, J. P., Garey, L. J. &Jen, L. S. (1994b) β-Amyloid precursor protein immunoreactivity in normally developing and axotomised rat retinas.First European Meeting on Glial Cell Function in Health and Disease, Heidelberg.

  • Cicerone, C. M., Green, D. G. &Fisher, L. J. (1979) Cone inputs to ganglion cells in hereditary retinal degeneration.Science 203, 1113–14.

    PubMed  Google Scholar 

  • Dowling, J. E. &Sidman, R. L. (1962) Inherited retinal dystrophy in the rat.Journal of Cell Biology 14, 73–109.

    PubMed  Google Scholar 

  • Edgington, S. M. (1994) As we live and breath: free radicals and aging.BioTechnology 12, 37–40.

    PubMed  Google Scholar 

  • Eisenfeld, A. J., Bunt-Milam, A. H. &Sarthy, P. V. (1984) Müller cell expression of glial fibrillary acidic protein after genetic and experimental photoreceptor degeneration in the rat retina.Investigative Ophthalmology and Visual Science 25, 1321–8.

    PubMed  Google Scholar 

  • Ekström, P., Sanyal, S., Narfström, K., Chader, G. J. &Van Veen, T. (1988) Accumulation of glial fibrillary acidic protein in Müller radial glia during retinal degeneration.Investigative Ophthalmology and Visual Science 29, 1363–71.

    PubMed  Google Scholar 

  • El-Hifnawi, E. (1987) Pathological changes in retinal vasculature associated with hereditary retinal dystrophy in RCS rats. InOcular Circulation and Neovascularization (edited byBenezra, D., Ryan, S. J., Glaser, B. M. &Murphy, R. P.) pp. 409–17. Dordrecht, Boston, Lancaster: Martinus Nijhoff/Dr W. Junk Publishers.

    Google Scholar 

  • El-Hifnawi, E. (1995) Localization of cathepsin D in rat ocular tissues. An immunohistochemical study.Annals of Anatomy 177, 11–17.

    Google Scholar 

  • El-Hifnawi, E. &Kühnel, W. (1987) The role of lysosomes in hereditary retinal dystrophy in RCS rats. InAdvances in Biosciences vol 62. Research in Retinitis Pigmentosa (edited byZrenner, E., Krastel, H. &Goebel, H.-H.) pp. 381–95. Pergamon Journals Ltd.

  • El-Hifnawi, E., Kühnel, P., El-Hifnawi, A. &Laqua, H. (1994) Localization of lysosomal enzymes in the retina and retinal pigment epithelium of RCS rats.Annals of Anatomy 176, 505–13.

    Google Scholar 

  • Fernaud-Espinosa, I., Nieto-Sampedro, M. &Bovolenta, P. (1993) Differential activation of microglia and astrocytes in aniso- and isomorphic gliotic tissue.Glia 8, 277–91.

    PubMed  Google Scholar 

  • Haass, C., Hung, A. Y. &Selkoe, D. J. (1991) Processing of β-amyloid precursor protein in microglia and astrocytes favors an internal localization over constitutive secretion.Journal of Neuroscience 11, 3783–93.

    PubMed  Google Scholar 

  • Hockenbery, D. M., Zutter, M., Hickey, W., Nahm, M. &Korsmeyer, S. J. (1991) Bcl-2 protein is topographically restricted in tissues characterized by apoptotic cell death.Proceedings of the National Academy of Sciences (USA) 88, 6961–5.

    Google Scholar 

  • Hockenbery, D. M., Oltvai, Z. N., Yin, X. M., Milliman, C. L. &Korsmeyer, S. J. (1993) Bcl-2 functions in an antioxidant pathway to prevent apoptosis.Cell 75, 241–51.

    PubMed  Google Scholar 

  • Jacobson, M. D., Burne, J. F., King, M. P., Miyashita, T., Reed, J. C. &Raff, M. C. (1993) Bcl-2 blocks apoptosis in cells lacking mitochondrial DNA.Nature 361, 365–9.

    PubMed  Google Scholar 

  • Jeon, C.-J. &Masland, R. H. (1993) Selective accumulation of diamidino yellow and chromomycin A3 by retinal glial cells.Journal of Histochemistry and Cytochemistry 41, 1651–8.

    PubMed  Google Scholar 

  • Kalaria, R. N., Bhatti, S. U., Palatinsky, E. A., Pennington, D. H., Shelton, E. R., Chan, H. W., Perry, G. &Lust, W. D. (1993) Accumulation of the β-amyloid precursor protein at sites of ischemic injury in rat brain.NeuroReport 4, 211–14.

    PubMed  Google Scholar 

  • Koo, E. H., Park, L. &Selkoe, D. J. (1993) Amyloid β-protein as a substrate interacts with extracellular matrix to promote neurite outgrowth.Proceedings of the National Academy of Sciences (USA) 90, 4748–52.

    Google Scholar 

  • Laties, A. M. (1983) New light on the Müller cell.Transactions of the Ophthalmological Society of the UK 103, 380–4.

    Google Scholar 

  • Laties, A. M. &Liebman, P. A. (1970) Cones of living amphibian eye: selective staining.Science 168, 1475–7.

    PubMed  Google Scholar 

  • Lavail, M. M. &Reif-Lehrer, L. (1971) Glutamine sythetase in the normal and dystrophic mouse retina.Journal of Cell Biology 51, 348–54.

    PubMed  Google Scholar 

  • Lebrun, D. P., Warnke, R. A. &Cleary, M. L. (1993) Expression ofbcl-2 in fetal tissues suggests a role in morphogenesis.American Journal of Pathology 142, 743–53.

    PubMed  Google Scholar 

  • Li, Z.-Y., Jacobson, S. G. &Milam, A. H. (1984) Autosomal dominant retinitis pigmentosa caused by the threonine-17-methionine rhodopsin mutation: retinal histopathology and immunocytochemistry.Experimental Eye Research 58, 397–408.

    Google Scholar 

  • Li, L., Sheedlo, H. J. &Turner, J. E. (1993) Müller cell expression of glial fibrillary acidic protein (GFAP) in RPE-cell transplanted retinas of RCS dystrophic rats.Current Eye Research 12, 841–9.

    PubMed  Google Scholar 

  • Linser, P. J., Sorrentino, M. &Moscona, A. A. (1984) Cellular compartmentalization of carbonic anhydrase-C and glutamine synthetase in developing and mature mouse neural retina.Developmental Brain Research 13, 65–71.

    Google Scholar 

  • Marks, N., Grynbaum, A. &Lajtha, A. (1976) The breakdown of myelin-bound proteins by intra- and extracellular protease.Neurochemical Research 1, 93–111.

    Google Scholar 

  • Mattson, M. P., Barger, S. W., Cheng, B., Lieberburg, I., Smith-Swintosky, V. L. &Rydel, R. E. (1993) β-Amyloid precursor protein metabolites and loss of neuronal Ca2+ homeostasis in Alzheimer's disease.Trends in Neurosciences 16, 409–14.

    PubMed  Google Scholar 

  • Merry, D. E., Veis, D. J., Hickey, W. F. &Korsmeyer, S. J. (1994) bcl-2 protein expression is widespread in the developing nervous system and retained in the adult PNS.Development 120, 301–11.

    PubMed  Google Scholar 

  • Morin, P. J., Abraham, C. R., Amaratunga, A., Johnson, R. J., Huber, G., Sandell, J. H. &Fine, R. E. (1993) Amyloid precursor protein is synthesized by retinal ganglion cells, rapidly transported to the optic nerve plasma membrane and nerve terminals, and metabolized.Journal of Neurochemistry 61, 464–73.

    PubMed  Google Scholar 

  • Mullen, R. J. &Lavail, M. M. (1976) Inherited retinal dystrophy: primary defect in pigment epithelium determined with experimental rat chimeras.Science 192, 799–801.

    PubMed  Google Scholar 

  • Nieto-Sampedro, M. &Mora, F. (1994) Active microglia, sick astroglia and Alzheimer type dementias.NeuroReport 5, 375–80.

    PubMed  Google Scholar 

  • Nishimoto, I., Okamoto, T., Matsuura, Y., Takahashi, S., Okamoto, T., Murayama, Y. &Ogata, E. (1993) Alzheimer amyloid protein precursor complexes with brain GTP-binding protein G0.Nature 362, 75–9.

    PubMed  Google Scholar 

  • Noell, W. K. (1965) Aspects of experimental and hereditary retinal degeneration. InBiochemistry of the Eye (edited byGraymore, C. N.) pp. 51–72. London: Academic Press.

    Google Scholar 

  • Reichelt, W., Dettmer, D., Brückner, G., Brust, P., Eberhardt, W. &Reichenbach, A. (1989) Potassium as a signal for both proliferation and differentiation of rabbit retinal (Müller) glia growing in cell culture.Cellular Signalling 1, 187–94.

    PubMed  Google Scholar 

  • Reichenbach, A. (1989) Attempt to classify glial cells by means of their process specialization using the rabbit retinal Müller cell as an example of cytotopographic specialization of glial cells.Glia 2, 250–9.

    PubMed  Google Scholar 

  • Reichenbach, A. &Birkenmeyer, G. (1984) Preparation of isolated Müller cells of the mammalian (rabbit) retina.Zeitschrift für mikroskopisch-anatomische Forschung 98, 789–92.

    Google Scholar 

  • Reichenbach, A. &Reichelt, W. (1986) Postnatal development of radial glial (Müller) cells of the rabbit retina.Neuroscience Letters 71, 125–30.

    PubMed  Google Scholar 

  • Reichenbach, A., Schneider, H., Leibnitz, L., Reichelt, W., Schaaf, P. &Schumann, R. (1989) The structure of rabbit retinal Müller (glial) cells is adapted to the surrounding retinal layers.Anatomy and Embryology 180, 71–9.

    PubMed  Google Scholar 

  • Reichenbach, A., Stolzenburg, J.-U., Eberhardt, W., Chad, T. I., Dettmer, D. &Hertz, L. (1993) What do retinal Müller (glial) cells do for their neuronal ‘small siblings’?Journal of Chemical Neuroanatomy 6, 201–13.

    PubMed  Google Scholar 

  • Reichenbach, A., Ziegert, M., Kasper, M., Schnitzer, J., Osborne, N. N., Pritz-Hohmeier, S., Schaaf, P., Schober, W. &Schneider, H. (1994) Development of the rabbit retina. V. The question of ‘columnar units’.Developmental Brain Research 79, 72–84.

    PubMed  Google Scholar 

  • Riepe, R. E. &Norenberg, M. D. (1977) Müller cell localization of glutamine synthetase in rat retina.Nature 268, 654–5.

    PubMed  Google Scholar 

  • Roque, R. S. &Caldwell, R. B. (1990) Müller cell changes precede vascularization of the pigment epithelium in the dystrophic rat retina.Glia 3, 464–75.

    PubMed  Google Scholar 

  • Sarthy, P. V. &Fu, M. (1988) Photoreceptor cell degeneration leads to induction of the glial intermediate filament protein gene in the mouse retina. InMolecular Biology of the Eye: Genes, Vision, and Ocular Disease (edited byPiatigorsky, J., Shinohara, T. &Zelenka, P. S.) pp. 305–15. New York: Alan R. Liss.

    Google Scholar 

  • Sarthy, P. V. &Lam, D. M. K. (1978) Biochemical studies of isolated glial (Müller) cells from the turtle retina.Journal of Cell Biology 78, 675–84.

    PubMed  Google Scholar 

  • Selkoe, D. J. (1994) Normal and abnormal biology of the β-amyloid precursor protein.Annual Reviews of Neuroscience 17, 489–517.

    Google Scholar 

  • Shaw, G. &Weber, K. (1983) The structure and development of the rat retina: an immunofluorescence microscopical study using antibodies specific for intermediate filament proteins.European Journal of Cell Biology 30, 219–32.

    PubMed  Google Scholar 

  • Siman, R., Card, J. P., Nelson, R. B. &Davis, L. G. (1989) Expression of β-amyloid precursor protein in reactive astrocytes following neuronal damage.Neuron 3, 275–85.

    PubMed  Google Scholar 

  • Stolzenburg, J.-U., Haas, J., Härtig, W., Paulke, B.-R., Wolburg, H., Reichelt, W., Chao, T. I., Wolff, J. R. &Reichenbach, A. (1992) Phagocytosis of latex beads by rabbit retinal Müller (glial) cellsin vitro.Journal für Hirnforschung 33, 557–64.

    Google Scholar 

  • Trapp, B. D. &Hauer, P. E. (1994) Amyloid precursor protein is enriched in radial glia: implications for neuronal development.Journal of Neuroscience Research 37, 538–50.

    PubMed  Google Scholar 

  • Turner, D. L. &Cepko, C. L. (1987) A common progenitor for neurons and glia persists in rat retina late in development.Nature 328, 131–6.

    PubMed  Google Scholar 

  • Wilcox, D. K. (1988) Vectorial accumulation of cathepsin D in retinal pigmented epithelium: effects of age.Investigative Ophthalmology and Visual Science 29, 1205–12.

    PubMed  Google Scholar 

  • Yamada, T., Hara, S. &Tamai, M. (1990) Immunohistochemical localization of cathepsin D in ocular tissues.Investigative Ophthalomology and Visual Science 31, 1217–23.

    Google Scholar 

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Härtig, W., Grosche, J., Distler, C. et al. Alterations of Müller (glial) cells in dystrophic retinae of RCS rats. J Neurocytol 24, 507–517 (1995). https://doi.org/10.1007/BF01179976

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