Pathologic changes in chronic intraorbital optic nerve damage in rabbits

To construct a chronic intraorbital optic nerve compression damage model in rabbits and investigate pathologic changes of the retina and optic nerve.

A balloon was implanted into the orbit of rabbits, in which contrast medium was filled at designated time points to simulate chronic tumor compression on the intraorbital optic nerve. Funduscopy, visual electrophysiology, histopathology, immunohistochemistry, apoptosis and gene assays were used to examine the changes of retinal ganglion cells (RGCs) and neuroglial cells, as well as the expression of ciliary neurotrophic factor (CNTF) and growth associated protein 43 (GAP-43) in each phase of the chronic intraorbital optic nerve damage (2, 4 and 8 weeks after modeling).

Funduscopic examination showed that there was no significant change in the optic disk in non-compression group; the optic disk was congested and edematous in 2 w-compression group, but with no significant change in color; in 4 w-compression group, edema was lessened but color became lighter; in 8 w-compression group, no edema was found but the color was pale. Flash visual evoked potential (FVEP) suggested that the change of FVEP wave forms was more obvious as the compression extended, especially the low, flat, wide and irregular wave forms; the latent period of P(1), N(1) and P(2) was prolonged and the amplitude became lower. Compared with the wave form in non-compression group, there was no significant difference in 2 w-compression group (P>0.05), but the differences were prominent in 4 w- and 8 w-compression groups (P<0.01). Histopathology checks indicated no changes in the retina and optic nerve in non-compression group; in 2 w-compression group, there were also no significant changes, but the cell number of optic nerve decreased, the fibers were deranged, and the bundle membrane was damaged; in 4 w-compression group, nuclei in the RGC layer became sparse, the cell number of optic nerve increased significantly, the optic nerve bundles were deranged; in 8 w-compression group, nuclei in the RGC layer remained sparse and disordered, in the optic nerve there were a large number of disordered and deranged cells, the structure of fiber bundles was not clear, the bundle membrane was incomplete. Immunohistochemistry results showed there was no obvious change in the content of glial fibrillary acidic protein (GFAP) in the optic nerve in non-compression group; its expression began increasing in 2 w-compression group and remained high level in 8 w-compression group. With the compression extending, the number of apoptotic cells in RGCs layer increased gradually, and it was positive correlation with the compression time. CNTF and GAP-43 expressions were low in blank control and non-compression groups, and were up-regulated in 2 w-compression group (P<0.01); with the compression extending, the expressions of two genes increased gradually (P<0.01).

A chronic intraorbital optic nerve compression damage model was constructed successfully, and in that way we found that with the compression extending, more RGCs were lost; the structure of optic nerve fibers was damaged; the number of neuroglial cells tended to decreased at the beginning and then increased; and the CNTF and GAP-43 expressions increased gradually 2 weeks after damage.