Anterior Ischemic Optic Neuropathy Alters RGC and Oligodendrocyte Function

Abstract

Abstract: : Purpose: To investigate the changes occurring in the retina and optic nerve (ON) in anterior ischemic optic neuropathy (AION), using a c-fos transgenic mouse model. Methods: AION was induced in mice as previously reported (Goldenberg-Cohen et al, 2002). We used a transgenic mouse line constructed with a c-fos promotor/LacZ reporter gene. C-fos activation was detected by blue cellular reaction. One eye was left untreated as an internal control. Post-AION induction, the ON and retina were assessed for morphological and functional changes. We utilized confocal microscopy with cell-specific antibodies to characterize the timing of cells responding to AION. TUNEL assay detected cells undergoing apoptosis. Ultrastructural changes were analyzed by electron microscopy. Results: C-fos activation is seen in retinal ganglion cells (RGCs) and oligodendrocytes. The oligodendrocyte response begins near the globe and proceeds retrogradely, across the chiasm. ON demyelination begins within 3 days. ON apoptosis begins posterior to the primary lesion. Thirty percent of RGCs are lost by day 21 post induction. Conclusions: Post-AION induction oligodendrocytes, as well as RGCs, undergo progressive stress, with dysfunction and apoptosis. Effective AION therapy may require a dual approach toward preserving not only RGCs but also oligodendrocytes.

Keywords: animal model • ischemia • neuro-ophthalmology: optic nerve