Morphometric and electrophysiological evidence for a diameter-based rate of degeneration in the optic nerve of the rat.

The diameter-based rate of degeneration in the rat's optic nerve was examined using coordinated morphological and electrophysiological techniques. Long-Evans, male rats were implanted with indwelling stimulating electrodes in the optic chiasm and recording electrodes in the stratum opticum of the superior colliculus. After 1 week, unilateral enucleation was performed with the unoperated side serving as the control. Electrically evoked recordings, obtained on the day of enucleation (D0), displayed three distinct peaks, Pre, N1 and P3, with peak latencies of 1.22, 2.22, and 4.04 ms, respectively. In a parallel set of rats, morphological analysis of the optic nerve over D1-7 was performed. Electron micrographs were taken of cross sections of the entire optic nerve from both the enucleated and unoperated (i.e., control) side. Computer-linked morphometric analysis of the ultrastructurally normal axons from each nerve was assembled in three-dimensional, diameter-based histograms at each time point. The control population consisted of axons with diameters ranging from less than 0.5-5.0 microns with a modal peak of 1.5 micron and a well developed tail in the 3.5-5.0 microns range. By D1,2, a selective loss of large diameter (greater than 3.5 microns) axons occurred in the optic nerve, with medium diameter (2.0-3.5 microns) axons degenerating at D4 and smaller diameter populations (less than 2.0 microns) persisting until later time points (D5-7). A linear regression analysis showed an exponential rate of degeneration which was a direct function of axonal diameter. In summary, this study demonstrates that the fiber population of the optic nerve is separable electrophysiologically and by its rate of degeneration, with larger diameter fibers degenerating faster in response to transection.