Cell and Tissue Research

, Volume 241, Issue 2, pp 241–249 | Cite as

Nerve fiber production by intraocular adrenal medullary grafts: Stimulation by nerve growth factor or sympathetic denervation of the host iris

  • Ingrid Strömberg
  • Ted Ebendal
  • Åke Seiger
  • Lars Olson


This study evaluates the production of adrenergic nerve fibers by adrenal medullary tissue of the adult rat grafted to the anterior chamber of the eye of adult recipients. The chromaffin grafts attach to and become vascularized by the host iris. They decrease in size intraocularly during the first 3 weeks. This decrease is somewhat counteracted by sympathetic denervation of the host iris, and better counteracted by sympathetic denervation and addition of nerve growth factor (NGF, given at grafting and 1 and 2 weeks after grafting). Outgrowth of adrenergic nerve fibers from the grafts into the host iris was studied in wholemount preparations by use of the Falck-Hillarp technique 3 weeks after grafting. The innervated area of the host iris was approximately doubled in the chronically sympathectomized group and doubled again in the chronically sympathectomized NGF-supplemented group. Chronic sympathetic denervation had no effect on density of outgrowing nerves, whereas addition of NGF more than doubled nerve density. Since sympathetic denervation causes a slight elevation of NGF activity in the iris, the present experiments are taken as evidence that the level of NGF in the iris regulates formation of nerve fibers by adrenal medullary tissue grafts from adult rats.

Key words

Chromaffin grafts Adrenal medulla Transplantation, intraocular Nerve growth factor Adrenergic nerves Denervation, sympathetic Nerve growth Rat 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Acheson AL, Naujoks K, Thoenen H (1984) Nerve growth factormediated enzyme induction in primary cultures of bovine adrenal chromaffin cells: Specificity and level of regulation. J Neurosci 4:1771–1780Google Scholar
  2. Aloe L, Levi-Montalcini R (1979) Nerve growth factor induced transformation of immature chromaffin cells in vivo into sympathetic neurons: Effect of antiserum to nerve growth factor. Proc Natl Acad Sci USA 76:1246–1250Google Scholar
  3. Ayer-LeLievre CS, Ebendal T, Olson L, Seiger Å (1983) Localization of nerve growth factor-like immunoreactivity in rat nervous tissue. Med. Biol. 61:296–304Google Scholar
  4. Ayer-LeLievre Ch, Ebendal T, Kessler J, Seiger Å (1985) Growth stimulation of grafted substance P-immunoreactive sensory ganglia induced by nerve growth factor (in preparation)Google Scholar
  5. Backlund E-O, Granberg PO, Hamberger B, Knutsson E, Mårtenson A, Sedvall G, Seiger Å, Olson L (1985) Transplantation of adrenal medullary tissue to striatum in parkinsonism. First clinical trials. J Neurosurg 62:169–173Google Scholar
  6. Backlund E-O, Granberg PO, Hamberger B, Sedvall G, Seiger Å, Olson L (1985) Transplantation of adrenal medullary tissue to striatum in parkinsonism. In: Björklund A, Stenevi U (eds) Neural grafting in the Mammalian CNS. Elsevier, Amsterdam pp 537–556Google Scholar
  7. Barth E-M, Korsching S, Thoenen H (1984) Regulation of nerve growth factor synthesis and release in organ cultures of rat iris. J Cell Biol 99:839–843Google Scholar
  8. Corrodi H, Jonsson G (1967) The formaldehyde fluorescence method for the histochemical demonstration of biogenic monoamines. A review on the methodology. J Histochem Cytochem 15:65–78Google Scholar
  9. Ebendal T, Olson L, Seiger Å, Hedlund K-O (1980) Nerve growth factors in the rat iris. Nature 286:25–28Google Scholar
  10. Ebendal T, Olson L, Seiger Å (1983) The level of nerve growth factor (NGF) as a function of innervation. A correlative radioimmunoassay and bioassay study of the rat iris. Exp Cell Res 148:311–317Google Scholar
  11. Ebendal T, Olson L, Seiger Å, Belew M (1984) Nerve growth factors in chick and rat tissues. In: Black IB (ed) Cellular and molecular biology of neuronal development. Plenum Press, New York pp 231–242Google Scholar
  12. Falck B, Hillarp N-Å, Thieme G, Torp A (1962) Fluorescence of catecholamines and related compounds condensed with formaldehyde. J Histochem Cytochem 10:348–354Google Scholar
  13. Freed W, Morihisa J, Spoor E, Hoffer B, Olson L, Seiger Å, Wyatt R (1981) Transplanted adrenal chromaffine cells in rat brain reduce lesion-induced rotational behaviour. Nature 292:351–352Google Scholar
  14. Freed WJ, Karoum F, Spoor HE, Morihisa JM, Olson L, Wyatt RJ (1983) Catecholamine content of intracerebral adrenal medulla grafts. Brain Res 269:184–189Google Scholar
  15. Freed W, Hoffer B, Olson L, Wyatt R (1984) Transplantation of catecholamine-containg tissues to restore the functional capacity of the damaged nigrostriatal system. In: Sladek J, Gash D (eds) Neuronal transplants, Development and function. Plenum Press, New York pp 125–165Google Scholar
  16. Harper GP, Pearce FL, Vernon CA (1976) Production of nerve growth factor by the mouse adrenal medulla. Nature 261:251–253Google Scholar
  17. Herrera-Marschitz M, Strömberg I, Olsson D, Olson L, Ungerstedt U (1984) Adrenal medullary implants in the dopamine-denervated rat striatum. II. Rotational behavior during the first seven hours as a function of graft amount and location and its modulation by neuroleptics. Brain Res 297:53–61Google Scholar
  18. Korsching S, Thoenen H (1983) Nerve growth factor in sympathetic ganglia and corresponding target organs of the rat: Correlation with density of sympathetic innervation. Proc Natl Acad Sci USA 80:3513–3516Google Scholar
  19. Levi-Montalcini R (1982) Developmental neurobiology and the natural history of nerve growth factor. Ann Rev Neurosci 5:341–362Google Scholar
  20. Naujoks KW, Korsching S, Rohrer H, Thoenen H (1982) Nerve growth factor-mediated induction of tyrosine hydroxylase and of neurite outgrowth in cultures of bovine adrenal chromaffin cells: Dependence on developmental stage. Dev Biol 92:365–379Google Scholar
  21. Olson L (1970) Fluorescence histochemical evidence for axonal growth and secretion from transplanted adrenal medullary tissue. Histochemie 22:1–7Google Scholar
  22. Olson L (1985) On the use of transplants to counteract the symptoms of Parkinson's disease: Background, experimental models and possible clinical applications. In: Carl Cotman (ed) Synaptic plasticity and remodelling Guilford Press pp 485–505Google Scholar
  23. Olson L, Malmfors T (1970) Growth characteristics of adrenergic nerves in the adult rat. Fluorescence histochemical and 3H-noradrenaline uptake studies using tissue transplantations to the anterior chamber of the eye. Acta Physiol Scand Suppl 348:1–112Google Scholar
  24. Olson L, Seiger Å (1983) Adrenergic nerve growth regulation: Nerve fiber formation by the superior cervical ganglion, the adrenal medulla, and locus coeruleus. Similarities and differences as revealed by grafting. In: Elfvin L-G (ed) Autonomic ganglia John Wiley and Sons Ltd., New York pp 507–522Google Scholar
  25. Olson L, Ungerstedt U (1970) A simple high capacity freeze-drier for histochemical use. Histochemie 22:8–19Google Scholar
  26. Olson L, Ebendal T, Seiger Å (1979) NGF and anti-NGF: Evidence against effects on fiber growth in locus coeruleus from cultures of perinatal CNS tissues. Dev Neurosci 2:160–176Google Scholar
  27. Olson L, Seiger Å, Ebendal T, Hoffer B (1980) Comparisons of nerve fiber growth from three major catecholamine producing cell systems; adrenal medulla, superior cervical ganglion and locus coeruleus. Third International Symposium on Nervous transmission. In: Eränkö O, Soinila S, Päivärinta H (eds) Histochemistry and cell biology of autonomic neurons, SIF cells and paraneurons. Raven Press New York pp 27–34Google Scholar
  28. Olson L, Seiger Å, Freedman R, Hoffer B (1980) Chromaffin cells can innervate brain tissue: Evidence from intraocular double grafts. Exptl Neurol 70:414–426Google Scholar
  29. Olson L, Hamberger B, Hoffer B, Miller R, Seiger Å (1981) Nervefiber formation by grafted adult adrenal medullary cells. In: Stjärne L, Hedqvist P, Lagercrantz H, Wennmalm Å (eds) Academic Press, London pp 35–48Google Scholar
  30. Olson L, Björklund H, Ebendal T, Hedlund K-O, Hoffer B (1981) Factors regulating growth of catecholamine-containing nerves, as revealed by transplantation and explantation studies. In: Elliott K, Lawrenson G (eds) Development of the autonomic nervous system. Ciba Foundation Symposium No. 83. Pitman Medical, London pp 213–226Google Scholar
  31. Olson L, Seiger Å, Strömberg I (1983) Intraocular transplantation in rodents. A detailed account of the procedure and examples of its use in neurobiology with special reference to brain tissue grafting. In: Fedoroff S, Hertz L (eds) Advances in cellular neurobiology, vol 4 Academic Press, New York pp 407–442Google Scholar
  32. Olson L, Backlund E-O, Freed W, Herrera-Marschitz M, Hoffer B, Seiger Å, Strömberg I (1985a) Transplantation of catecholamine-producing cell systems in oculo and intracranially: Experiments in search of a treatment for Parkinson's disease. In: Nottebohm F (ed) Hope for a new neurology. Ann NY Acad Sci (in press)Google Scholar
  33. Olson L, Backlund E-O, Sedvall G, Herrera-Marschitz M, Ungerstedt U, Strömberg I, Hoffer B, Seiger Å (1984) Intrastriatal chromaffin grafts in experimental and clinical Parkinsonism: first impressions. Proc 5th Intern Catechol Symp In: Usdin E, Carlsson A, Dahlström A, Engel J (eds) Catecholamines. Part C. neuropharmacology and central nervous system — Therapeutic aspects. (Neurology and Neurobiology, vol 8C). Alan R Liss, New York pp 195–201Google Scholar
  34. Olson L, Björklund H, Hoffer B (1984) Camera bulbi anterior: New vistas on a classical locus for neural tissue transplantation. In: Sladek J, Gash D (eds) neuronal transplants, development and function. Plenum Press, New York pp 373–406Google Scholar
  35. Olson L, Strömberg I, Herrera-Marschitz M, Ungerstedt U, Ebendal T (1985) Adrenal medullary tissue grafted to the dopamine-denervated rat striatum. In: Björklund A, Stenevi U (eds.) Neural grafting in the Mammalian CNS. Elsevier, Amsterdam pp. 505–518Google Scholar
  36. Seiger Å, Ebendal T, Olson L (1985) Level of nerve growth factor in the rat iris following treatment with capsaicin. (to be publ)Google Scholar
  37. Strömberg I, Herrera-Marschitz M, Hultgren L, Ungerstedt U, Olson L (1984) Adrenal medullary implants in the dopamine-denervated rat striatum. I. Acute catecholamine levels in grafts and host caudate as determined by HPLC-electrochemistry and fluorescence histochemical image analysis. Brain Res 297:41–51Google Scholar
  38. Strömberg I, Herrera-Marschitz M, Ungerstedt U, Ebendal T, Olson L (1985) Chronic implants of chromaffine tissue into the dopamine-denervated striatum. Effects of NGF on survival, fiber growth and rotational behavior (to be publ.)Google Scholar
  39. Tischler AS, DeLellis RA, Biales B, Nunnemacher G, Carabba V, Wolfe HJ (1980) Nerve growth factor-induced neurite outgrowth from normal human chromaffin cells. Lab Invest 43:399–409Google Scholar
  40. Tischler AS, Greene LA (1980) Phenotypic plasticity of pheochro-mocytoma and normal adrenal medullary cells. In: Eränkö O et al. (eds) Histochemistry and cell biology of autonomic neurons, SIF cells, and paraneurons. Raven Press, New York, pp 61–68Google Scholar
  41. Tischler AS, Perlman RL, Nunnemacher G, Morse GM, DeLellis RA, Wolfe HJ, Sheard BE (1982) Long-term effects of dexamethasone and nerve growth factor on adrenal medullary cells cultured from young adult rats. Cell Tissue Res 225:525–542Google Scholar
  42. Unsicker K (1983) Cell and tissue culture studies on the sympath-oadrenal system. In: Elfvin LG (ed) Autonomic ganglia. John Wiley, London, pp 475–505Google Scholar
  43. Unsicker K, Chamley J (1977) Growth characteristics of postnatal rat adrenal medulla in culture. Cell Tissue Res 177:247–268Google Scholar
  44. Unsicker K, Habura-Fluh O, Zwarg U (1978) Different types of small granule-containing cells and neurons in the guinea-pig adrenal medulla. Cell Tissue Res 189:109–130Google Scholar
  45. Unsicker K, Krisch B, Otten U, Thoenen E (1978) Nerve growth factor induced fiber outgrowth from isolated rat adrenal chromaffin cells: Impairment by glucocorticoids. Proc Natl Acad Sci USA 75:3498–3502Google Scholar
  46. Unsicker K, Rieffert B, Ziegler W (1980) Effects of cell culture conditions, nerve growth factor, dexamethasone, and cyclic AMP on adrenal chromaffin cells in vitro. In: Eränkö O et al. (eds) Histochemistry and cell biology of autonomic neurons, SIF cells, and paraneurons. Raven Press, New York, pp 51–59Google Scholar
  47. Unsicker K, Millar TJ, Hofmann HD (1982) Nerve growth factor requirement of postnatal rat adrenal medullary cells in vitro for survival, aggregate formation and maintenance of extended neurites. Dev Neurosci 5:412–417Google Scholar
  48. Ziegler W, Hofmann HD, Unsicker K (1983) Rat adrenal non-chromaffin cells contain a neurite outgrowth-promoting factor immunologically different form nerve growth factor. Dev Brain Res 7:353–357Google Scholar

Copyright information

© Springer-Verlag 1985

Authors and Affiliations

  • Ingrid Strömberg
    • 1
  • Ted Ebendal
    • 1
    • 2
  • Åke Seiger
    • 1
  • Lars Olson
    • 1
  1. 1.Department of HistologyKarolinska InstitutetStockholmSweden
  2. 2.Department of ZoologyUppsala UniversityUppsalaSweden

Personalised recommendations