Abstract
Purpose :
Although non-arteritic AION (NAION) is the most common cause of sudden optic nerve-related vision loss, the pathologic changes from primary optic nerve damage to retinal ganglion cell (RGC) death are not evident. Here we describe the ultrastructural changes in the optic nerve of rAION model to plot the pathology of AION progression.
Methods :
rAION was induced (n=35) in adult male Wistar rats using photodynamic therapy. Optical coherence tomography (OCT) was performed to validate the rAION. Pathologic changes were observed in the acute (6 hour, day-1 and day-3), subacute (day-7), and chronic (day 14 and day 28) phases. Transmission electron microscopy (TEM) of the optic nerve (ON) cross sections (80nm) was done to visualize ultrastructural changes. Immunohistochemistry of glial fibrary acidic protein (GFAF), vimentin, myelin basic protein (MBP), ionized calcium-binding adapter molecule 1 (Iba1), and hematoxylin & eosin (HE) staining was performed to validate our TEM findings.
Results :
Compared with sham animals, severe astrocyte swelling, myelin damage, blood-optic nerve barrier (BOB) breakdown, severe vacuolation was observed during the acute phase. In the sub-acute phase, the BOB was restored and astrocyte swelling was reduced. We found some axon degeneration along with myelin damage. In chronic phase, we observed mild astrocyte swelling, severe axon degeneration and microglia phagocytosis of damaged myelin and other debris. GFAP and Vimentin expression in the cell body of astrocytes was increased in the acute phase and chronic phase. The expression of MBP was also decreased in the chronic phase of AION indicating myelin degeneration.Moreover, HE stain confirmed optic nerve atrophy. Our data suggest that astrocytes reactivity first occurs when the BOB is ruptured. Once the BOB is restored, the astrocyte reactivity is also reduced. The second episode occurs during chronic phase because of ongoing inflammatory process, degenerating-myelin and -axon.
Conclusions :
After rAION induction, the optic nerve showed significant ultrastructure changes marked by BOB disruption, astrocyte swelling, myelin damage, axon degeneration, microglia phagocytosis, and vacuolation. Our observations suggest that modulation of astrocyte and preserving BOB in the acute phase may halt the anterograde axon degeneration and RGC death.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.