Cellular organisation of the optic nerve and the implications for optic neuritis


Opportunities for studying growth, degeneration and repair in the central nervous system have altered over the last decade with the development of techniques for cul-turing neurones and glia and the availability of immun-ological or molecular markers that identify separate lineages and their progeny. Much pioneering work has been carried out in the rodent optic nerve but the principles that emerge are representative for other parts of the nervous system; development of neurones and glia may differ substantially in rats and man, so that assumptions must be made in extrapolating from properties of the rat optic nerve to diseases of the human central nervous system.


  1. 1

    Perry VH and Gordon S : Macrophages and microglia in the nervous system. Trends Neurosci 1988, 11: 273–7.

  2. 2

    Bjorklund A ed: Transplantation in the nervous system. Trends Neurosci 1991, 14: 319–88.

  3. 3

    Cameron RS and Rakic P : Glial cell lineage in the cerebral cortex: a review and synthesis. Glia 1991, 4: 124–37.

  4. 4

    Misson J-P, Takahashi T, Caviness VS : Ontogeny of radial and other astroglial cells in the murine cerebral cortex. Glia 1991, 4: 138–48.

  5. 5

    Raff MC, Miller RH, Noble M : A glial progenitor that develops in vitro into an astrocyte or an oligodendrocyte depending on culture medium. Nature 1983, 303: 390–2.

  6. 6

    Miller RH, ffrench Constant C, Raff MC :. The macroglial cells of the rat optic nerve. Ann Rev Neurosci 1989, 12: 517–34.

  7. 7

    ffrench Constant C, Raff MC : Proliferating bipotential glial progenitor cells in adult rat optic nerve. Nature 1986, 319: 499–502.

  8. 8

    Noble M, Murray K, Stroobant P, Waterfield MD, Riddle P : Platelet derived growth factor promotes division and motil-ity and inhibits premature differentiation of the oligoden-drocyte/type 2 astrocyte progenitor cell. Nature 1988, 333: 560–2.

  9. 9

    Noble M : Points of controversy in the 0-2A lineage: clocks and type 2 astrocytes. Glia 1991, 4: 157–64.

  10. 10

    Hart IK, Richardson WD, Heldin CH, Westermark B, Raff MC : PDGF receptors on cells of the oligodendrocyte-type 2 astrocyte (0-2A) cell lineage. Development 1989, 105: 595–604.

  11. 11

    Hart IK, Richardson WD, Bolsover SR, Raff MC : PDGF and intracellular signalling in the timing of oligodendrocyte differentiation. J Cell Biol 1989, 109: 3411–17.

  12. 12

    Miller RH, Fulton BP, Raff MC : A novel type of glial cell associated with nodes of Ranvier in rat optic nerve. Eur J Neurosci 1989, 1: 172–80.

  13. 13

    Skoff RP, Knapp PE : Division of astroblasts and oligo-dendroblasts in postnatal rodent brain: evidence for separate astrocyte and oligodendrocyte lineages. Glia 1991, 4: 165–74.

  14. 14

    Butt AM and Ransom BR : Visualisation of oligodendrocytes and astrocytes in the intact rat optic nerve by intracellular injection of Lucifer yellow and horseradish peroxidase. Glia 1991, 2: 470–5.

  15. 15

    Goldmann JE and Vaysse PJ-J : Tracing glial cell lineages in the mammalian forebrain. Glia 1991, 4: 149–56.

  16. 16

    Wolswijk G and Noble M : Identification of an adult specific glial progenitor cell. Development 1989, 105: 387–400.

  17. 17

    Prineas JW, Kwon EE, Goldenberg PZ, Ilyas AA, Quarles RH, Benjamins JA, Sprinkle TJ : Multiple Sclerosis. Oligo-dendrocyte Proliferation and Differentiation in fresh lesions. Lab Invest 1989, 61: 489–503.

  18. 18

    Armstrong R, Friedrich VL, Holmes KV, Dubois-Dalcq M : In vitro analysis of the oligodendrocyte lineage in mice during demyelination and remyelination. J Cell Biol 1990, 111: 1183–95.

  19. 19

    Godfraind C, Friedrich VL, Holmes KV, Dubois-Dalcq M : In vivo analysis of glial cell phenotypes during viral demyelinating disease in mice. J Cell Biol 1989, 109: 2405–16.

  20. 20

    Carroll WM, Jennings AR, Mastaglia FL : The origin of remyelinating oligodendrocytes in antiserum-mediated demyelinative optic neruropathy. Brain 1990, 113: 953–73.

  21. 21

    Fawcett JW and Housden E : The effects of protease inhibitors on axon growth through astrocytes. Development 1990, 109: 59–66.

  22. 22

    Fawcett JW, Rokos J, Bakst I : Oligodendrocytes repel axons and cause axonal growth cone collapse. J Cell Sci 1989, 92: 93–100.

  23. 23

    Fawcett JW, Housden E, Smith-Thomas L, Myer RL : The growth of axons in 3 dimensional astrocyte cultures. Dev Biol 1989, 135: 449–58.

  24. 24

    Caroni P and Schwab ME : Two membrane protein fractions from rat central myelin with inhibitory properties for neurite growth and fibroblast spreading. J Cell Biol 1988, 106: 1281–88.

  25. 25

    Caroni P and Schwab ME : Antibody against myelin associated inhibitor of neurite growth neutralises non-permissive substrate properties of CNS white matter. Neuron 1988, 1: 85–96.

  26. 26

    Schnell L and Schwab ME : Axonal regeneration in the rat spinal cord produced by an antibody against myelin associated neurite growth inhibitors. Nature 1990, 343: 269–72.

  27. 27

    Wiktorin K, Brundin P, Gustavi B, Lindvall O, Bjorklund A : Reformation of long axon pathways in adult rat central nervous system by human forebrain. Nature 1990, 347: 556–8.

  28. 28

    Stern CD, Sisodiya SM, Keynes RJ (1986): Interactions between neurites and somite cells: inhibition and stimulation of nerve growth in the chick embryo. J Embryol Exp Morph 1986, 91: 209–26.

  29. 29

    Male, DK, Pryce G, Hughes CCW, Lantos PL : Lymphocyte migration into the brain modelled in vitro: control by lymphocyte activation, cytokines and antigen. Cell Immunol 1990; 127: 1–11.

  30. 30

    Hickey WF : Migration of hematogenous cells through the blood brain barrier and the initiation of CNS inflammation. Brain Pathol 1991, 1: 97–105.

  31. 31

    Scolding NJ, Morgan BP, Houston WAJ, Campbell AK, Linington C, Compston DAS : Normal rat serum cytotoxic-ity against syngeneic oligodendrocytes: complement activation and attack in the absence of antimyelin antibodies. J Neurol Sci 1989, 89: 289–300.

  32. 32

    Wren DR and Noble M : Oligodendrocytes and adult specific 0-2A progenitor cells are uniquely susceptible to the lytic effects of complement in the absence of antibody. Proc Natl Acad Sci 1989, 86: 9025.

  33. 33

    Wing MG, Zajicek JP, Seilly DJ, Compston DAS, Lachmann PJ : Inhibition of antibody-dependent classical pathway activation by oligodendrocytes using CD59. Immunology 1992 (in press).

  34. 34

    Zajicek JP, Wing M, Lachmann PJ, Compston DAS : Oligodendrocyte interactions with human serum—the simultaneous demonstration of antibody independent classical pathway complement activation and abnormal sensitivity to terminal complement attack. J Neuro Sci 1992 (in press).

  35. 35

    Scolding NJ, Morgan BP, Campbell AK, Compston DAS : The role of calcium in rat oligodendroctye injury and repair. Neurosci Lett 1992 (in press).

  36. 36

    Scolding NJ, Morgan BP, Houston WAJ, Linington C, Campbell AK, Compston DAS (1989). Vesicular removal by oligodendrocytes of membrane attack complexes formed by complement. Nature 1989 339, 620–2.

  37. 37

    Scolding NJ and Compston DAS : Oligodendrocye macrophage interactions in vitro triggered by specific antibodies. Immunology 1991, 72: 127–32.

  38. 38

    Compston DAS, Morgan BP, Campbell AK, Wilkins P, Cole G, Thomas ND, Jasani B : Immunocytochemical localisation of the terminal complement complex in multiple sclerosis. Neuropath and Appl Neurobiol 1989, 15: 307–316.

  39. 39

    Compston DAS, Scolding NJ, Wren DR, Noble M : The pathogenesis of demyelinating disease: insights from cell biology. Trends Neurosci 1991, 14: 175–82.

  40. 40

    Shaw PJ, Smith NM, Ince PG, Bates D : Chronic periph-lebitis retinae in multiple sclerosis. A histological study. J Neurol Sci 1987, 77: 142–52.

  41. 41

    Lightman S, McDonald WI, Bird AC, Francis DA, Hoskins A, Batchelor JR, Halliday AM : Retinal venous sheathing in optic neuritis. Its significance for the pathogenesis of multiple sclerosis. Brain 1987, 110: 405–14.

  42. 42

    Miller DH, McDonald WI, Blumhardt LD, du Boulay GH, Halliday AM, Johnson G, Kendall BE, Kingsley DPE, Mac-Manus DG, Moseley IF, Rudge P, Sandercock PAG : Magnetic resonance imaging in isolated spinal cord syndromes. Ann Neurol 1987, 22: 714–23.

  43. 43

    Miller DH, Newton MR, van der Poel JC : Magnetic resonance imaging of the optic nerve in optic neuritis. Neurology 1988, 38: 175–9.

  44. 44

    Youl BD, Miller DH, MacManus DG, Moore SG, Barnes D, Kermode AG, Hawkins CP, Kendall BE, Moseley IF, Tofts PS, Thompson AJ, McDonald WI : Optic nerves show gadolinium enhancement in early optic neuritis. Neuroradiol 1991, 33 [Suppl]: 129–30.

  45. 45

    Youl BD, Turano G, Miller DH, Towell AD, MacManus DG, Moore SG, Jones SJ, Barrett G, Kendall BE, Moseley IF, Tofts PS, Halliday AM, McDonald WI : The pathophy-siology of acute optic neuritis: an association of gadolinium leakage with clinical and electrophysiological deficits. Brain 1992, 114: 2437–50.

  46. 46

    Kermode AG, Thompson AJ, Tofts P, MacManus GG, Kendall BE, Kingsley DPE, Moseley IF, Rudge PR, McDonald WI : Breakdown of the blood brain barrier precedes symptoms and other MRI signs of new lesions in multiple sclerosis. Brain 1990, 113: 1477–89.

  47. 47

    Miller DH, Rudge PR, Johnson G, Kendall BE, MacManus DG, Moseley IF, Barnes D, McDonald WI : Serial gadolinium enhanced magnetic resonance imaging in multiple sclerosis. Brain 1988, 111: 927–39.

  48. 48

    Koopmans RA, Li DKB, Oger J J-F, Mayo J, Paty DW : The lesions of multiple sclerosis: imaging of acute and chronic stages. Neurol 1989, 39: 959–63.

  49. 49

    Sanders EACM and van Lith GHM : Optic neuritis, confirmed by visual evoked response, and the risk for multiple sclerosis: a prospective study. J Neurol Neurosurg Psych 1989, 52: 799–800.

  50. 50

    Parkin PJ, Hierons R, McDonald WI : Bilateral optic neuritis: a long term follow-up. Brain 1984, 106: 951–64.

  51. 51

    Rizzo JF and Lessell S : Risk of developing multiple sclerosis after uncomplicated optic neuritis: a long term prospective study. Neurology 1988, 38: 185–90.

  52. 52

    Sandberg-Wollheim S, Bynke H, Cronqvist S, Holtas S, Platz P, Ryder LP : A long term prospective study of optic neuritis: evaluation of risk factors. Ann Neurol 1990, 27: 386–93.

Download references

Author information

Correspondence to Alastair Compston.

Rights and permissions

Reprints and Permissions

About this article

Further reading