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Abstract
Vinblastine sulfate (VLB; 1 to 500 µg in 10 to 50 µd of saline) was injected into the vitreous of the right eyes of adult, albino rabbits. Equal volumes of saline were infected into the left eyes as control eyes. The animals were killed after periods of 15, 30, and 60 minutes, 4 hours, 1, 7, and 14 days, and 8 weeks, and the retinae were examined by electron microscopy. No recognizable morphologic changes were produced in the retinal ganglion cells (GC's) by injection of saline or 1 to 6 µg of VLB. VLB (10 µg)produced a decrease in the number of intact microtubules (MT's) in the GC soma and processes by one hour, with a normal number of MT's again observed at seven days. Nearly all MT's were lost from the GC's one hour after doses of 25 to 500 µg of VLB. With the 25 µg dose, scattered intact MT's were again present at 14 days and by eight weeks an apparently normal number of MT's was observed. Very few recognizable MT's were present even at eight weeks following injection of 100 fig or more of VLB. To study rapid axonal transport in the GC's, 20 µCi of 3H-proline was injected into each eye at various intervals after injection of 1 to 500 µg of VLB and saline as above. Comparative scintillation counts of the superior colliculi at 24 hours following isotope injection revealed that rapid axonal transport was inhibited by exposure of the retina to 10 to 500 µg of VLB at least one hour before isotope injection. Blockage of transport was reversed by 14 days following the 10 µg VLB dose but did not appear to be reversible even at eight weeks after a dose of 25 µg or more. These results support previous suggestions that intact MT's are required for rapid axonal transport, although in the case of retinal GC's it appears that the transport process may remain blocked when morphologically normal MT's are again present in the axons. The present finding that a low (10 µg) dose of VLB can reversibly block rapid transport in the retinal GC's will provide a useful model for the study of postulated trophic effects of GC axons in the visual system.