Evidence for a Role of NGF in the Visual System

  • Maria Cristina Comelli
  • Paola Candeo
  • Roberto Canella
  • Adalberto Merighi
  • Lamberto Maffei
  • Giorgio Carmignoto
Part of the NATO ASI Series book series (NSSA, volume 222)


It is generally accepted that the development, maintenance and survival of specific neuronal populations, both in the peripheral (PNS) and central nervous system (CNS), is dependent upon the supply of diffusable trophic molecules, produced in limiting amounts by neurons and/or glia in their target fields (for review, see Thoenen et al., 1987). The prototype of neuronotrophic factors, Nerve Growth Factor (NGF) is essential for neural crest-derived sensory and peripheral symphathetic neurons (Levi -Montalcini and Angeletti, 1968) and for cholinergic neurons of forebrain nuclei in the CNS (Hefti, 1986; Vantini et al., 1989). In all these NGF-responsive peripheral and central neurons, NGF binds to specific cell surface receptors (NGFRs) expressed both on cell bodies and axonal terminals in the innervated target area (Greene and Shooter, 1980). The immunocytochemical mapping of the NGFR with the 192-IgG monoclonal antibody (Chandler et al., 1984) has demonstrated that the receptor is expressed by many different neuronal population in the CNS (Yan and Johnson, 1989; Pioro and Cuello, 1990), suggesting that NGF, or an NGF-like molecule have a trophic role for many other cell types beyond the cholinergic ones. The first evidence that NGF may also be active in the visual system was obtained in the early eighties when it was demonstrated that NGF, when intraocularly supplied to axotomized retinal ganglion cells (RGCs) in the goldfish, enhanced the process of axonal regneration in the transected optic nerve (ON). More recent studies (Yan et al., 1989; Pioro and Cuello, 1990) have demonstrated that the NGFR is expressed in many nuclei of the visual system receiving a retinal input both in developing and adult rats.


Nerve Growth Factor Retinal Ganglion Cell Inner Nuclear Layer Nerve Growth Factor Receptor Monocular Deprivation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Berardi, N., Carmignoto, G., Domenici, L., and Maffei, L., 1990, The intraventricular NGF injections prevents the effects of monocular deprivation in the rat, J. Physiol., 422:9P.Google Scholar
  2. Berardi, N., Carmignoto, G., Cremisi, F., Domenici, L., Maffei, L., Parisi, V., and Pizzorusso, T., 1991, NGF prevents the change in ocular dominance distribution induced by monocular deprivation in the rat visual cortex, J. Physiol., 434:14P.Google Scholar
  3. Carmignoto, G., Maffei, L., Candeo, P., Canella, R., and Comelli, C., 1989, Effect of NGF on the survival of rat retinal ganglion cells following optic nerve section, J. Neurosci., 9:1263.PubMedGoogle Scholar
  4. Carmignoto, G., Candeo, P., Comelli, M.C., Calderini, G., and Maffei, L., 1990, Expression of Nerve Growth Factor Receptor (NGFR) on adult rat retinal ganglion cell (RGC) terminals. 20th Annual Meeting of The Society for Neuroscience, Abstract 343. 19.Google Scholar
  5. Carmignoto, G., Comelli, M.C., Candeo, P., Cavicchioli, L., Yan, Q., Merighi, A., and Maffei, L., 1991, Expression of NGF Receptor and NGF Receptor mRNA in the developing and adult rat retina, Exp Neurol., 111: 302.PubMedCrossRefGoogle Scholar
  6. Carmignoto, G., Canella R., Candeo P., and Comelli M.C., 1991, Expression of NGF receptor by retinal ganglion cells in the adult rat, Proceeding 5th World Congress of Biological Psychiatry, Florence, 9–14 June, 1991, Excerpta Medica International Congress Series, in press.Google Scholar
  7. Chandler, C.E, Parsons, L.M., Hosang, H., and Shooter E.M., 1984, A monoclonal antibody modulates the interactions of Nerve Growth Factor to PC12, J. Biol. Chem., 259:6882.PubMedGoogle Scholar
  8. Chao, M.V., Bothwell, M.A., Ross, A.H., Koprowski, H., Lanahan, A.A., Buck, C.R., and Sehgal, A., 1986, Gene transfer and molecular cloning of the human NGF receptor, Science, 232: 518.PubMedCrossRefGoogle Scholar
  9. Comelli, M.C., Bonfanti, L., Merighi, A., Carmignoto, G., and Maffei, L. 1990, The expression of Nerve Growth Factor Receptor (NGFR) mRNA is developmentally regulated and increased after optic nerve section, 20th Annual Meeting of the Society for Neuroscience, Abstract 343. 18.Google Scholar
  10. Ernfors, P., Ibànez, C.F., Ebendal, T., Olson, L., and Persson, H., 1990, Molecular cloning and neurotrophic activities of a protein with structural similarities to nerve growth factor: developmental and topographical expression in the brain, Proc. Natl. Acad. Sci. USA, 87:5454.PubMedCrossRefGoogle Scholar
  11. Greene, L.A., and Shooter, E.M., 1980, The nerve growth factor: biochemistry, synthesis and mechanism of action, Annu. Rev. Neurosci., 3:353.PubMedCrossRefGoogle Scholar
  12. Hall, S. and Berry, M., 1989, Electron microscopy study of the interaction of axons and glia at the site of anastomosisi between the optic nerve and cellular or acellular sciatic nerve grafts, J. Neurocytol., 18: 171–184.PubMedCrossRefGoogle Scholar
  13. Hefti, F., 1986, Nerve growth factor promotes the survival of septal cholinergic neurons after fimbrial transections, J. Neurosci., 6:2155.PubMedGoogle Scholar
  14. Hempstead, B.L., Martin-Zanca, D., Kaplan, D.R., Parada, L.F., and Chao, M.V., 1991, High affinity NGF binding requires coexpression of the trk proto-oncogene and the low affinity NGF receptor, Nature, 350: 678.PubMedCrossRefGoogle Scholar
  15. Hubel, D.H., Wiesel, T.N., LeVay, S., 1977, Plasticity of ocular dominance columns in monkey striate cortex, Phil. Trans. R. Soc. B., 278:377.PubMedCrossRefGoogle Scholar
  16. Johnson, E.M., Osborne, P.A., Taniuchi, M., 1989, Destruction of sympathetic and sensory neurons in the developing rat by a monoclonal antibody against the nerve growth factor ( NGF) receptor, Brain Res., 478: 166–170.PubMedCrossRefGoogle Scholar
  17. Kaplan, D.R., Hempstead, B., Martin-Zanca, D., Chao, M.V., and Parada, L.F., 1991, The trk proto-oncogene product: a signal transducing receptor for Nerve Growth Factor, Science, 252: 554.PubMedCrossRefGoogle Scholar
  18. Klein, R., Parada, L.F., Coulier, F., and Barbacid, M., 1989, trkB, a novel tyrosine protein kinase receptor expressed during mouse neural development, The EMBO J., 8(12):3701.Google Scholar
  19. Large, T.H., Weskamp, G., Helder, J.C., Radeke, M.J., Misko, T.P., Shooter, E.M., and Reichardt, L.F., 1989, Structure and developmental expression of the nerve growth factor receptor in the chicken central nervous system, Neuron, 2: 1123.PubMedCrossRefGoogle Scholar
  20. Levi-Montalcini, R., and Angeletti, P.U., 1968, Nerve growth Factor, Physiol Rev., 48: 534.PubMedGoogle Scholar
  21. Maisonpierre, P.C., Belluscio, L., Friedman, B., Alderson, R.F., Wiegand, S.J., Furth, M.E., Lindsay, R., and Yancopoulos, G.D., 1990, NT-3, BDNF, and NGF in the developing rat nervous system: parallel as well as reciprocal patterns of expression, Neuron, 5: 501.PubMedCrossRefGoogle Scholar
  22. Meakin, S.O., and Shooter, E.M., 1991, Molecular investigations on the high-affinity nerve growth factor receptor, Neuron, 6: 153.PubMedCrossRefGoogle Scholar
  23. Paradiso, M.A., Bear, M.F., Daniels, J.D., 1983, Effects of intra-cortical infusion of 6-Hydroxy-dopamine on the response of kittens visual cortex to monocular deprivation, Exp. Brain Res., 51:413.CrossRefGoogle Scholar
  24. Pioro, P., and Cuello, A.C., 1990, Distribution of nerve growth factor receptor-like immunoreactivity in the adult rat central nervous system. Effect of colchicine and correlation with the cholinergic system-I. Forebrain, Neuroscience, 1: 57.CrossRefGoogle Scholar
  25. Purves, D., 1988, Body and Brain. A trophic theory of neural connections. Cambridge, MA: Harvard University Press.Google Scholar
  26. Radeke, M.J., Misko, T.P., Hsu, C., Herzenberg, L.A., and Shooter, E.M., 1987, Gene transfer and molecular cloning of the rat nerve growth factor, Nature, 325: 593.PubMedCrossRefGoogle Scholar
  27. Richardson, P.M., Issa, V.M. and Shemie, S., 1982, Regeneration and retrograde degeneration of axons in the rat optic nerve, J. Neurocytol., 11:949–966.PubMedCrossRefGoogle Scholar
  28. Rodriguez-Tebar, A., Dechant, G., and Barde, Y.A., 1990, Binding of brain-derived neurotrophic factor to the nerve growth factor receptor, Neuron, 4: 487.PubMedCrossRefGoogle Scholar
  29. Siliprandi, R., Canella, R., Comelli, M.C., Zanoni, R., and Carmignoto, G., 1990, Nerve Growth Factor (NGF) effects on the function of cat retinal ganglion cells following ischemia, Invest. Opthalmol. Vis. Sci., 31(Suppl):139.Google Scholar
  30. Schatteman, G.C., Gibbs, L., Lanahan, A.A., Claude, P., and Bothwell, M., 1988, Expression of NGF receptor in the developing and adult primate central nervous system, J. Neurosci., 8:860.PubMedGoogle Scholar
  31. Thoenen, H., Bandtlow, C., and Heumann, R., 1987, The physiological function of nerve growth factor in central nervous system: comparison with the periphery, Rev. Physiol. Pharmacol., 109:145.CrossRefGoogle Scholar
  32. Turner, J.E., Delaney, R.K., and Johnson, J.E., 1980, Retinal ganglion cell response to nerve growth factor in the regenerating, and intact visual system of the goldfish (“carassius auratus”), Brain Res., 197: 319.PubMedCrossRefGoogle Scholar
  33. Yan, Q., and Johnson, E.M. Jr, 1989, Immunohistochemical localization and biochemical characterization of nerve growth factor receptor in adult rat brain, J. Comp. Neurol., 290:585.PubMedCrossRefGoogle Scholar
  34. Yip, H.K., and Grafstein, B., 1982, Effect of nerve growth factor on regeneration of goldfish optic axons, Brain Res., 238: 329.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1991

Authors and Affiliations

  • Maria Cristina Comelli
    • 1
  • Paola Candeo
    • 1
  • Roberto Canella
    • 1
  • Adalberto Merighi
    • 2
  • Lamberto Maffei
    • 3
  • Giorgio Carmignoto
    • 1
  1. 1.Fidia Research LaboratoriesAbano TermeItaly
  2. 2.Dipartimento di Morfofisiologia VeterinariaUniversità di TorinoTorinoItaly
  3. 3.Istituto di Neurofisiologia del CNRPisaItaly

Personalised recommendations