Ultrastructural changes induced in the rat retina by treatment with colchicine

Colchicine, 0.05 g to 10 g dissolved in 1 l water, was injected in the vitreous body in the eye of adult albino rats. The animals were fixed by perfusion via the aorta or by immersion at varying time intervals and examined by electron microscopy.Ultrastructural changes were observed within a few hours after intraocular injection of 0.2 g colchicine. All the different types of retinal cells showed a common main mode of reaction. The nucleolus appeared to increase in size and density during the first days. The chromatine became dispersed and the components in the nucleus increased. Rodlets of 70 Å filaments appeared in an increased number of the nuclei of the neuroectodermal cells. The number of cell organelles increased i.e. mitochondria, lysosomes, ribosomes arranged as polyribosomes, in the vicinity of the nuclear infoldings. The profiles of the endoplasmic reticulum became short and tubulo-saccular. The number of filaments increased only in those cells which normally are rich in that structure.The retinal nerve cells in the ganglion cell layer and inner nuclear layer showed signs of disintegration of their Nissl substance but no proliferation of filaments. No apparent changes were observed with regard to the neurotubuli in these neurons. Many synaptic bodies degenerated and several nerve cell processes were retracted. There was an accumulation of especially synaptic vesicles in the distended terminals.The inner segments of the photoreceptor cells were retracted and became filled with amorphous material. The outer segments decreased gradually in length during the first week and only a rudiment remained thereafter. The Müller neuroglial cells showed a marked increase in the number of filaments and a slight of the tubuli.The ultrastructural findings are discussed especially with respect to the mechanisms of intracellular transport. It is proposed that the heavy increase in the number of filaments in nerve cells in certain regions of the nervous system does reflect an inbalance between formation and intracellular transport of filaments. The possibility is discussed that colchicine inhibits not only the cytoplasmic but also the intranuclear transport of cell constituents.This study was supported by grants from the Swedish Medical Research Council (B71-12X-2543-03 and B71-13X-2226-05) and Riksföreningen mot Cancer (265-B70-02X).