Changes in retinal ganglion cell axons after optic nerve crush: neurofilament expression is not the sole determinant of calibre

Abstract

After injury in the central nervous system of adult mammals, many of the axons that remain attached to their intact cell bodies degenerate and decrease in calibre. To understand this process better, we have investigated the relationship between axonal loss, cell loss, and the time course of changes in axonal calibre. Optic nerves (ONs) were crushed and the numbers and sizes of axons remaining close to the cell bodies (2 mm from the eye) and near the site of the lesion (6 mm from the eye) were determined for nerves examined between 1 week and 3 months after injury. Comparison with the retinal ganglion cell (RGC) counts from the same animals revealed that axonal loss was concomitant with cell body loss for at least the first 2 weeks after injury. However, there was no significant change in the calibre of the surviving neurons until 1 month after injury. Thereafter, the axonal calibre was decreased equally along the ON. No progressive somatofugal atrophy was observed. These decreases in axonal calibre occur much later than the immediate drop in neurofilament (NF) expression that also follows injury. The late effect of injury on axonal calibre suggests that NF expression is not the sole determinant of axon size of the RGC fibers in the ON. Other factors are likely additional contributing factors, such as the decreased rate of axonal transport that would help maintain the axonal neurofilament content.

Dynamic behavior and organization of cytoskeletal proteins in neurons: reconciling old and new findings

“…Decreased caliber of about 40-45% begins at proximal levels of the regenerating stump and is later also seen at a more distal level, consistent with the possibility that this percentage of the total neurofilament has been transported anterogradely out of the atrophied portions of the axon. Under the same conditions of suppressed NF synthesis, the smaller ventral motor axons (32) and all transected optic axons (33) undergo no change in caliber or neurofilament content, as predicted if most neurofilaments in these axons are stationary. Based on previous data.…”

“…Based on previous data. (32,33) isotypes undergoing transport is much smaller than the preexisting (and presumably stationary) pool in the axon.…”

“…Transected optic axons also behave this way. (33) In these two studies, the preservation of normal caliber in the face of reduced neurofilament supply to the axon implies that most Figure 3. Neurofilaments pulse-radiolabeled in vivo disappear from optic axons at two different rates, consistent with the behavior depicted in Figure 2.…”

Rodent Models for Glaucoma Retinopathy and Optic Neuropathy

“…Optic nerve crush induced injury to the optic nerve and loss of viable axons, [185][186][187] which led to retrograde degeneration of RGC in the rat and mouse. Depending on the force used during the crush, a wide spectrum of RGC damage, ranging from practically no change in cell density to almost complete elimination of the cells within 30 days, were achieved.…”

Rat Optik Sinir Ezme Modelinde Topikal ve Sistemik Alfa Tokoferol Uygulaması Yoluyla Retina Gangliyon Hücre Korunması

“…It has been shown that optic nerve crush induces optic nerve injury and causes retrograde degeneration of RGC of the rat. 17 Optic nerve crush model is easy to perform and it causes slow RGC loss that is much more similar to the nature of glaucoma than that of optic nerve transection model. Optic nerve damage may be induced by crushing optic nerve with clamps, forceps or other mechanic devices.…”