Inhibition of axoplasmic transport in the developing visual system of the rat-L Structural changes in the retina and optic nerve with graded doses of intraocular colchicine.

In order to study the role of axonal transport in the mediation of transneuronal metabolic stimulations upon a population of differentiating neurons, colchicine, a potent inhibitor of rapid and slow phases of axonal transport, was injected into the eye of albino rats at 1, 3, 5, 10, 15 and 20 days postnatal in concentrations ranging from 10-5 M to 2 X 10-2 M and in quantities of 0.3 to 0.5 microliter. Quantitative light and electron microscopy were subsequently employed to assess reactive alterations in the developing retina and optic nerve. Application of colchicine severely retarded the development of the sensory elements, with disappearance of synaptic ribbons of sensory cell axons, a significant reduction in the thickness of the inner plexiform layer, due to the presence of numerous shruken synaptic elements and the appearance of rosettes of sensory cells displaced to the inner nuclear layer. These alterations were found to be dose-dependent. Counts of ganglion cell populations at various times after application of colchicine demonstrated optimal concentrations which could be injected at each postnatal age without causing ganglion cell degeneration. Ultrastructural examination of such cells revealed varying degrees of disorganization and dissolution of the endoplasmic reticulum with the formation of occasional small cytoplasmic vacuoles. Higher concentrations of colchicine caused extensive vacuole formation in all classes of retinal neurons, scattered hyperchromic cells and widespread degeneration and autolysis. The diameter of the optic nerve was reduced to 60-95% of normal following intraocular colchicine, depending on the concentration employed, but electron microscopy revealed normal patterns of distribution of axoplasmic microtubules and filaments in control and experimental animals and quantitative analysis revealed no significant loss of axons. While no reactive changes took place in individual elements, the periphery of the nerve was often indented by a highly-folded glia limitans. Maximal doses of intraocular colchicine for each age level were established by this study. These were: 1 day. 10-3 M: 5 days, 5 x 10-3 M; 10 days, 5 X 10-3 M; 15 and 20 days, 10-2 M. The information derived from this morphological analysis provides the foundation for subsequent measurements of axonal transport inhibition in the developing visual system to be reported in the second article of this series.