Retinal changes induced by treatment with vincristine and vinblastine

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.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).