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. 1984 Jun;3(6):1287–1293. doi: 10.1002/j.1460-2075.1984.tb01964.x

Early regenerative responses induced by monoclonal antibodies directed against a surface glycoprotein of goldfish retinal ganglion cells.

M Schwartz, N Eshhar
PMCID: PMC557510  PMID: 6204857

Abstract

Monoclonal antibodies directed primarily against antigenic determinants associated with the goldfish optic nerve were prepared and characterized. One selected clone 23-4-C(IgG2a), detected antigenic determinants of glycoprotein nature with an apparent mol. wt. of 140 000. Following injury the level of these molecules increased with a peak at 5-7 days after the lesion (2- to 3-fold higher than the basal level). The results strongly suggest that the increase derives, at least partially, from a real increment in the level of these molecules in the retinal ganglion cells rather than from changes in accessibility. Immunofluorescence studies indicate that the retinal ganglion cells carry the antigenicity. Intraocular injection of the monoclonal antibodies, concomitantly with crush injury, resulted in an earlier and higher regenerative response, reflected by sprouting capacity, protein synthesis and accumulation of radiolabeled material in the tectum contralateral to the side of injury. This may indicate that the antibodies directly activate retinal cells via interaction with surface molecules. Alternatively, the antibodies may be directed against surface molecules which are associated with axonal growth inhibitors, and may therefore mask these surface antigens from further interaction with their native substrate.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Barnstable C. J. Monoclonal antibodies which recognize different cell types in the rat retina. Nature. 1980 Jul 17;286(5770):231–235. doi: 10.1038/286231a0. [DOI] [PubMed] [Google Scholar]
  2. Benowitz L. I., Shashoua V. E., Yoon M. G. Specific changes in rapidly transported proteins during regeneration of the goldfish optic nerve. J Neurosci. 1981 Mar;1(3):300–307. doi: 10.1523/JNEUROSCI.01-03-00300.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brackenbury R., Thiery J. P., Rutishauser U., Edelman G. M. Adhesion among neural cells of the chick embryo. I. An immunological assay for molecules involved in cell-cell binding. J Biol Chem. 1977 Oct 10;252(19):6835–6840. [PubMed] [Google Scholar]
  4. Eisenbarth G. S., Walsh F. S., Nirenberg M. Monoclonal antibody to a plasma membrane antigen of neurons. Proc Natl Acad Sci U S A. 1979 Oct;76(10):4913–4917. doi: 10.1073/pnas.76.10.4913. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Eshhar Z., Ofarim M., Waks T. Generation of hybridomas secreting murine reaginic antibodies of anti-DNP specificity. J Immunol. 1980 Feb;124(2):775–780. [PubMed] [Google Scholar]
  6. Giulian D., Des Ruisseux H., Cowburn D. Biosynthesis and intra-axonal transport of proteins during neuronal regeneration. J Biol Chem. 1980 Jul 10;255(13):6494–6501. [PubMed] [Google Scholar]
  7. Goldowitz D., Cotman C. W. Axonal transport and axon sprouting in the adult rat dentate gyrus: an autoradiographic study. Neuroscience. 1980;5(12):2163–2174. doi: 10.1016/0306-4522(80)90133-5. [DOI] [PubMed] [Google Scholar]
  8. Grafstein B., Forman D. S. Intracellular transport in neurons. Physiol Rev. 1980 Oct;60(4):1167–1283. doi: 10.1152/physrev.1980.60.4.1167. [DOI] [PubMed] [Google Scholar]
  9. Grafstein B. The nerve cell body response to axotomy. Exp Neurol. 1975 Sep;48(3 Pt 2):32–51. doi: 10.1016/0014-4886(75)90170-3. [DOI] [PubMed] [Google Scholar]
  10. Griffin J. W., Price D. L., Drachman D. B., Morris J. Incorporation of axonally transported glycoproteins into axolemma during nerve regeneration. J Cell Biol. 1981 Jan;88(1):205–214. doi: 10.1083/jcb.88.1.205. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hausman R. E., Moscona A. A. Immunologic detection of retina cognin on the surface of embryonic cells. Exp Cell Res. 1979 Mar 15;119(2):191–204. doi: 10.1016/0014-4827(79)90348-3. [DOI] [PubMed] [Google Scholar]
  12. Heacock A. M., Agranoff B. W. Protein synthesis and transport in the regenerating goldfish visual system. Neurochem Res. 1982 Jun;7(6):771–788. doi: 10.1007/BF00965529. [DOI] [PubMed] [Google Scholar]
  13. Henke-Fahle S., Bonhoeffer F. Inhibition of axonal growth by a monoclonal antibody. Nature. 1983 May 5;303(5912):65–67. doi: 10.1038/303065a0. [DOI] [PubMed] [Google Scholar]
  14. Hoffman P. N., Lasek R. J. Axonal transport of the cytoskeleton in regenerating motor neurons: constancy and change. Brain Res. 1980 Dec 8;202(2):317–333. doi: 10.1016/0006-8993(80)90144-4. [DOI] [PubMed] [Google Scholar]
  15. Jacobs S., Chang K. J., Cuatrecasas P. Antibodies to purified insulin receptor have insulin-like activity. Science. 1978 Jun 16;200(4347):1283–1284. doi: 10.1126/science.663609. [DOI] [PubMed] [Google Scholar]
  16. Kohsaka S., Schwartz M., Agranoff B. W. Increased activity of ornithine decarboxylase in goldfish following optic nerve crush. Brain Res. 1981 Jun;227(3):391–401. doi: 10.1016/0165-3806(81)90076-6. [DOI] [PubMed] [Google Scholar]
  17. Köhler G., Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature. 1975 Aug 7;256(5517):495–497. doi: 10.1038/256495a0. [DOI] [PubMed] [Google Scholar]
  18. Landreth G. E., Agranoff B. W. Explant culture of adult goldfish retina: a model for the study of CNS regeneration. Brain Res. 1979 Jan 26;161(1):39–55. doi: 10.1016/0006-8993(79)90194-x. [DOI] [PubMed] [Google Scholar]
  19. Landreth G. E., Agranoff B. W. Explant culture of adult goldfish retina: effect of prior optic nerve crush. Brain Res. 1976 Dec 17;118(2):299–303. doi: 10.1016/0006-8993(76)90714-9. [DOI] [PubMed] [Google Scholar]
  20. McQuarrie I. G., Grafstein B. Effect of a conditioning lesion on optic nerve regeneration in goldfish. Brain Res. 1981 Jul 20;216(2):253–264. doi: 10.1016/0006-8993(81)90128-1. [DOI] [PubMed] [Google Scholar]
  21. Murray M. 3 H-uridine incorporation by regenerating retinal ganglion cells of goldfish. Exp Neurol. 1973 Jun;39(3):489–497. doi: 10.1016/0014-4886(73)90033-2. [DOI] [PubMed] [Google Scholar]
  22. Murray M., Forman D. S. Fine structural changes in goldfish retinal ganglion cells during axonal regeneration. Brain Res. 1971 Sep 24;32(2):287–298. doi: 10.1016/0006-8993(71)90325-8. [DOI] [PubMed] [Google Scholar]
  23. Murray M., Grafstein B. Changes in the morphology and amino acid incorporation of regenerating goldfish optic neurons. Exp Neurol. 1969 Apr;23(4):544–560. doi: 10.1016/0014-4886(69)90124-1. [DOI] [PubMed] [Google Scholar]
  24. Raff M. C., Fields K. L., Hakomori S. I., Mirsky R., Pruss R. M., Winter J. Cell-type-specific markers for distinguishing and studying neurons and the major classes of glial cells in culture. Brain Res. 1979 Oct 5;174(2):283–308. doi: 10.1016/0006-8993(79)90851-5. [DOI] [PubMed] [Google Scholar]
  25. Schachner M., Ruberg M. Z., Carnow T. B. Histological localization of nervous-system antigens in the cerebellum by immunoperoxidase labeling. Brain Res Bull. 1976 Jul-Aug;1(4):367–377. doi: 10.1016/0361-9230(76)90030-7. [DOI] [PubMed] [Google Scholar]
  26. Skene J. H., Willard M. Axonally transported proteins associated with axon growth in rabbit central and peripheral nervous systems. J Cell Biol. 1981 Apr;89(1):96–103. doi: 10.1083/jcb.89.1.96. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Skene J. H., Willard M. Changes in axonally transported proteins during axon regeneration in toad retinal ganglion cells. J Cell Biol. 1981 Apr;89(1):86–95. doi: 10.1083/jcb.89.1.86. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Thiery J. P., Brackenbury R., Rutishauser U., Edelman G. M. Adhesion among neural cells of the chick embryo. II. Purification and characterization of a cell adhesion molecule from neural retina. J Biol Chem. 1977 Oct 10;252(19):6841–6845. [PubMed] [Google Scholar]
  29. Trisler G. D., Schneider M. D., Nirenberg M. A topographic gradient of molecules in retina can be used to identify neuron position. Proc Natl Acad Sci U S A. 1981 Apr;78(4):2145–2149. doi: 10.1073/pnas.78.4.2145. [DOI] [PMC free article] [PubMed] [Google Scholar]

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