Vincristine-induced changes in the retina of the isolated arterially-perfused cat eye.
We have attempted to determine in this study whether the arterial administration of vincristine produces in cat the functional defects associated with hereditary and vincristine-induced night blindness in man. Using the isolated perfused cat eye, it has been possible to mimic some of the essential features of human night blindness, namely, retention of normal rhodopsin chemistry and normal photoreceptor activity, with marked suppression of the ERG b-wave. In addition, we find that vincristine produces an early, rapid fall in the c-wave, a potential that arises largely in the pigment epithelium. Ultrastructurally, it appears that many classes of retinal neuron are affected by the drug, but the principal changes in cytoarchitecture are seen in the photoreceptors. Except for the outer segments, paracrystalline deposits were found in all parts of the visual cell. The disruption of the normal microtubular organization of these cells suggests that the drug interferes with the functional integrity of the transport system by which synaptic activity is maintained. By reducing the efficacy of communication between visual cells and their second-order neurons, the electrical responses of post-synaptic elements is degraded. The route by which vinca alkaloids reach the neural retina is still uncertain, but our preliminary studies using HRP indicate that the relatively high concentration of vincristine used in this study may be responsible for compromising the blood-retinal barrier.
Ripps
H
H
Lions Eye Research Institute, Chicago, IL.
Mehaffey
L
L
Siegel
I M
IM
Niemeyer
G
G
D000818:Animals; D001813:Blood-Retinal Barrier / Q000187:drug effects; D002415:Cats; D004596:Electroretinography; D008854:Microscopy, Electron; D010477:Perfusion; D012160:Retina / Q000187:drug effects* / Q000503:physiopathology / Q000648:ultrastructure; D014750:Vincristine / Q000633:toxicity*
D014750:Vincristine