Retinal ganglion cell response to axotomy in the regenerating visual system of the newt ( Triturus viridescens): An ultrastructural morphometric analysis

Abstract

The neuronal perikaryal response to axotomy in the retinal ganglion cell layer of the newt ( Triturus viridescens) is a rapid and dramatic phenomenon. The earliest morphological changes are found in the nucleus and are prominent by 4 to 7 days postaxotomy (DPA). At that time, axotomized neurons begin to exhibit a dramatic chromatin pattern change from a heterochromatic to a euchromatic state. In addition, large multiple nucleoli are often seen in reactive nuclei, where one small nucleolus may infrequently be found in nuclei of intact controls. The passage of the ganglion cells through the various stages of nuclear reactivity can be plotted temporally. By 14 DPA the number of retinal ganglion cells demonstrating reactive nuclei and prominent nucleoli has reached a peak which continues through 21 DPA but thereafter declines returning to control conditions by 90 DPA. Only 50% to 60% of neurons within the retinal ganglion layer enter the reactive nuclear stages in response to axotomy. Therefore, a clear distinction can be made at the light microscopic level between reactive and nonreactive neurons with respect to changes in nuclear morphology. Neuronal perikaryal changes appearing later in response to axotomy can be demonstrated by electron microscopic morphometric analysis. By 7 DPA the only quantitatably significant changes are increases in the number and size of nucleoli per cell. However, by 14 DPA reative neurons show significant nuclear and cytoplasmic hypertrophy compared to intact controls and 7-DPA animals. In addition, significant increases in numbers of mitochondria, Golgi fields, and nucleoli were quantitated. Increases in bound and unbound ribosomes and nerotubules were also observed by 14 DPA.