The spatiotemporal pattern of somal and axonal pathology after perikaryal excitotoxic injury to retinal ganglion cells: A histological and morphometric study

Objective: To describe the spatiotemporal pattern of somal and axonal pathologic changes after perikaryal excitotoxic injury to retinal ganglion cells in-vivo. Methods: 40 male Sprague-Dawley rats were killed at 0 h, 24 h, 72 h and 7 days after injecting 20 nM N-methyl-D-aspartate (NMDA) into the vitreous chamber of left eye. Saline-injected right eyes served as control. After perfusion fixation, the eyes and retrobulbar optic nerves from half of the animals in each group were embedded in paraffin and tissues from the other half embedded in resin. Paraffin-embedded eyes and resin-embedded proximal (intraorbital) and distal (intracranial) optic nerve segments were evaluated by light microscopy. Light microscopic photographs of proximal and distal optic nerve segments were compared using the following parameters: axon counts, axonal swellings and myelin changes. Results: Retinas showed cell loss in ganglion cell layer (GCL) and reduction in inner retinal thickness at 72 h after NMDA injection (p < 0.05), with changes becoming more advanced after 7 days (p < 0.00 1). The cell count in GCL correlated strongly with the axonal counts (R = 0.929, p < 0.00 1). Axon loss, axon swellings and myelin damage were seen in both proximal and distal segments of optic nerves 72 h post-NMDA exposure (p<0.05), with changes increasing further at 7 days (p < 0.00 1). Pathological changes were more prominent in the distal segments (P < 0.05). Conclusion: Excitotoxic perikaryal injury causes an axonopathy, which is synchronous with the somal degeneration and which is most prominent in the distal portions of the axon, consistent with dying-back like neuropathy. (C) 2007 Elsevier Inc. All rights reserved.