Abstract
The mitosis-inhibiting Vinca-alkaloids vincristine sulphate and vinblastine sulphate were injected into the vitreous body. This treatment resulted in ultrastructural changes in the retina within an hour. The retinal nerve cells showed a marked increase in the number of cell organelles, including the 100 Å filaments found in their perikarya. The microtubules disappeared and crystalloid structures appeared within an hour. The axons became distended by accumulated cell organelles, usually surrounding a crystalloid. The synaptic bodies, especially the presynaptic ones, often contained crystalloids, and showed a transient increase in the number of synaptic vesicles. The inner segments of the photoreceptor cells showed similar ultrastructural alterations, and, in addition, stacks of membranous structures. The outer segments decreased in length, and only rudiments of these structures remained one week after the intravitreal injection. The non-pigmented epithelial cells and the Müller's neuroglial cells also showed marked structural alterations.
These ultrastructural changes are consistent with the biochemical and fluorescence microscopic observations that vincristine and vinblastine both inhibit the intracellular flow of cell constituents, as previously demonstrated to be the case with colchicine. It is proposed that the structural changes in the individual cells reflect the drug-induced imbalance between the inhibited intracellular transport and the continued formation of the cell constituents characteristic of the afflicted cell.
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References
babel, j., a.bischoff & h.spoendelin. Ultrastructure of the peripheral nervous system and sense organs. Atlas of normal and pathological anatomy. Stuttgart, G. Thieme Verlag (1970).
bensch, k. g. & s. e.malawista. Microtubular crystals in mammalian cells. J. Cell Biol. 40: 95–107 (1969).
bhisey, a. n. & j. j.freed. Ameboid movement induced in cultured macrophages by colchicine or vinblastine. Exp. Cell Res. 64: 419–428 (1971).
hansson, h.-a. A histochemical study of retinal changes induced by treatment with colchicine. Exp. Eye Res. 12: 198–209 (1971).
— & j.sjöstrand. Ultrastructural changes induced in the rat retina by treatment with colchicine. Doc. Ophthal., 31 (1): 29–63 (1972).
hendrickson, a. e. & w. m.cowan. Changes in the rate of axoplasmic transport during postnatal development of the rabbit's optic nerve and tract. Exp. Neurol. 30: 403–422 (1971).
hirano, a. & h. m.zimmerman. Some effects of vinblastine implantation in the cerebral white matter. Lab. Invest. 23: 358–367 (1970).
hökfelt, t. & a.dahlström. Effects of two mitosis inhibitors (colchicine and vinblastine) on the distribution and axonal transport of noradrenaline storage particles, studied by fluorescence and electron microscopy. Z. Zellforsch., 119: 460–482 (1971).
journey, l. j., j.burdman & p.george. Ultrastructural studies on tissue culture cells treated with vincristine (NCS - 67574). Cancer Chemotherapy Rep. 52: 509–517 (1968).
karlsson, j.-o., h.-a.hansson & j.sjöstrand. Effect of colchicine on axonal transport and morphology of retinal ganglion cells. Z. Zellforsch. 15: 265–283 (1971).
— & j.sjöstrand. The effect of colchicine on the axonal transport of protein in the optic nerve and tract of the rabbit. Brain Res. 13: 617–619 (1969).
— & — Rapid intracellular transport of fucose-containing glycoproteins in retinal ganglion cells. J. Neurochem., 18: 2209–2216 (1971).
karnovsky, n. j. A formaldehyde-glutaraldehyde fixative of high osmolarity for use in electron microscopy. J. Cell Biol. 27: 137 A (1965).
kreutzberg, g. w. Neuronal dynamics and axonal flow. IV. Blockage of intra-axonal enzyme transport by colchicine. Proc. Nat. Acad. Sci. (Wash.) 62: 722–728 (1969).
krishan, a. & d.hsu. Observations on the association of helical polyribosomes and filaments with vincristine - induced crystals in Earle's L-cell fibroblasts. J. Cell Biol. 43: 553–563 (1969).
krishan, a., d.hsu & p.hutchins. Hypertrophy of granular endoplasmic reticulum and annulate lamellaei in Earle's L-cells exposed to vinblastine sulphate. J. Cell Biol. 39: 211–213 (1968).
kristenson, k., e.lycke & j.sjöstrand. Spread of herpes simplex virus in peripheral nerves. Acta neuropath. 17: 44–51 (1971).
lampert, p. w., m. h.vogel & l. e.zimmerman. Pathology of the optic nerve in experimental acute glaucoms. Invest. Ophthal. 7: 199–211 (1968).
norström, a., h.-a.hansson & j.sjöstrand. Effects of colchicine on axonal transport and ultrastructure of the hypothalamo-neurohypophyseal system of the rat. Z. Zellforsch. 113: 271–294 (1971).
peters, a., s. l.palay & h. de f.webster. The fine structure of the nervous system. The cells and their processes, New York (1970). Hoeber Medical Division, Harper and Row Publ.
schlote, w. Nervus opticus und experimentelles Trauma. Berlin, 1970. Springer Verlag.
schochet, s. s. Jr., p. w.lampert & k. m.earle. Neuronal changes induced by intrathecal vincristine sulphate. J. Neuropath. exp. Neurol. 27: 645–658 (1968).
schonbach, j., ch.schonbach & m.cuenod. Rapid phase of axoplasmic flow and synaptic proteins: An electron microscopical autoradiographic study. J. comp. Neurol. 141: 485–498 (1971).
shelanski, m. l. & h.wisniewski. Neurofibrillary degeneration induced by vincristine therapy. Arch. Neurol. 20: 199–306 (1969).
sjöstrand, j. & h.-a.hansson. Effect of colchicine on the transport of axonal protein in the retinal ganglion cells of the rat. Exp. Eye Res., 12: 261–269 (1971).
straatsma, b. r., m. O.hall, r. a.allen & f.crescitelli. The retina. Los Angeles, 1969. University of California Press.
terry, r. d., h.visniewski & a. b.johnson. Studies on the formation of autophagic vacuoles in neurons treated with spindle inhibitors (colchicine and vinblastiine). J. Neuropath. exp. Neurol. 29: 142–151 (1969).
weiss, p. Neuronal dynamics and neuroplasmic (axonal) flow. In: Cellular dynamics of the neuron. Barondes s. h. (Ed.). New York, Academic Press, P. 3 (1969).
white, j. g. Effects of colchicine and Vinca-alkaloids on human platelets. Amer. J. Pathol. 53: 281–289 (1968).
wisniewski, h., r. d.terry & a.hirano. Neurofibrillary pathology. J. Neuropath. exp. Neurol. 29: 163–176 (1970).
young, r. w. The renewal of photoreceptor cell outer segments. J. Cell Biol. 33: 61–72 (1967).
— & b.droz. The renewal of protein in retinal rods and cones. J. Cell Biol. 39: 169 (1968).
zelena, j. Bidirectional shift of mitochondria in axons after injury. In: Cellular dynamics of the neuron. Barondes, S. H. (Ed.) New York, Academic Press. p. 73 (1969).
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This study was supported by grants from M. Bergwalls Stiftelse, W. and M. Lundgrens Stiftelse, H. Hiertas Stiftelse, Swedish Medical Research Council (B 72-12 X-2543-04 A) and the Swedish National Cancer Society (265 - B 70-02 X).
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Hansson, HA. Retinal changes induced by treatment with vincristine and vinblastine. Doc Ophthalmol 31, 65–88 (1972). https://doi.org/10.1007/BF00167362
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DOI: https://doi.org/10.1007/BF00167362