Regeneration of optic nerve fibers following graded injuries in rats

Abstract

To investigate the changes of retinal ganglion cell (RGC) and their axons, and nerve regeneration ability following graded optic nerve injury (ONI) in rats. A pair of cross-action forceps with 148.0 g clipping pressure was used to clip rat optic nerves for 3, 6, 12, 30 and 60 s to induce graded ONI animal model. The RGC was counted at 0.5, 1, 2, 3 and 7 months and the axons were observed 1, 2 and 3 months post-injury. The regeneration process was observed by transmission electron microscopy. The number of optic nerve fibers in transverse sections was calculated in silver-stained longitudinal sections, and a regeneration index (RI) was calculated based on these numbers. The RI, reflecting the regeneration ability of injured optic nerves, was calculated as follows: (number of nerve fibers 0.5 mm behind injury site-number of nerve fibers 2.5 mm behind injury site)/(number of nerve fibers 0.5 mm retrobulbarly-number of nerve fibers 2.5 mm behind injury site). RGC and axons lost continuously after partial ONI. The loss of RGC was fitted with exponential pattern consisted of two phases, acute losing phase within first two weeks post injury and followed by another phase characterized by slowly reducing of RGC. The loss ratio of RGC increased and the survival ratio decreased with the severity of injury intensity. The loss of RGC and axons was aggregated in severe injury and showed a self-limited trend in mild injury. A large amount of clustered, zonal unmyelinated regeneration fibers were present after injury. The RI was 1.409, 1.490, 0.916, 1.119 and 1.224 following 3, 6, 12, 30 and 60 s clipping injury (chi2 = 281.2, P < 0.01), respectively. Different RI was associated to different injury intensity, with a greater regeneration ability in mild injury. The secondary reaction and regeneration ability vary with graded intensity of optic nerve injury. A self-limited secondary reaction and a more powerful regeneration ability are associated with a mild injury. The repair behavior and the injury may reach a balance and result in a successful regeneration after a certain degree of injury.