Molecular events associated with increased regenerative capacity of the goldfish retinal ganglion cells following X-irradiation: decreased level of axonal growth inhibitors

Abstract

In our previous work we established conditions to study the contribution of non-neuronal cells to the process of goldfish optic nerve regeneration. This issue has been studied successfully by adapting the use of X-irradiation to manipulate division of non-neuronal cells associated with the injured nerve. The regenerative capacity of the goldfish retinal ganglion cells was determined subsequent to the X-ray treatment. In this work we present an analysis of the molecular events associated with regeneration and enhanced regenerative capacity which follows X-irradiation. Under normal conditions the non-neuronal cells surrounding an intact nerve released axonal growth inhibitors, the level of which was only slightly sensitive to X-irradiation. In contrast, regenerating nerves showed a marked decrease in substances having an inhibitory effect on sprouting in vitro. Moreover, their level was significantly reduced following X-irradiation which was accompanied by increased accumulation of fibrous collagen adjacent to astrocytes. The alteration in the reciprocal relationship between the axon and the surrounding non-neuronal cells was also manifested by changes in the profile of labeled proteins released by the non-neuronal cells. The results of this work, therefore, indicate the sensitivity of retinal ganglion cells to the environment provided by the cells surrounding the regenerating fibers and thus may open a new perspective relating to the capacity of neurons to regenerate.