Glial reaction to nerve growth factor in the regenerating optic nerve of the newt ( Triturus viridescens)

Abstract

Nerve growth factor (NGF), administered as a single intraocular injection at the time of nerve transection, elicited cellular hyperplasia and hypertrophy in the astrocyte-like glial cell population of the regenerating newt ( Triturus viridescens) optic nerve at 14 days postlesion. More specifically, there was a significant dose-dependent increase in the number of glial cells in response to various NGF concentrations [2 to 2000 biologic units (BU)], which correlated directly with the dose-dependent rise in the neuronal (regenerating axons) area of 14-day regenerating nerve cross sections. We refer to this phenomenon (i.e., cell hyperplasia) as a NGF dose-dependent glial cell response. Quantitation of the astrocyte-like cell perikaryal area and nuclear area, and calculation of cell: nuclear ratios indicated that cell hypertrophy was elicited by the 2000-BU dose of NGF, but not by lower NGF concentrations (i.e., 2 to 200 BU). Corroborative ultrastructural observations were even more revealing. Not only did electron micrographs verify cellular hypertrophy in the astrocyte-like glial cells, but also they revealed hypertrophy of cell processes and a massive increase in the number of microfilaments in response to the 2000-BU NGF treatment. We speculate that these phenomena may represent an NGF dose-independent glial cell response.