Abstract
Purpose: :
Posterior Ischemic optic neuropathy (PION) is a sight devastating disease in clinical practice. However its pathogenesis and natural history has remained poorly understood. The purpose of this study was to develop a reliable, reproducible animal model of PION and test the treatment effect of neurotrophic factors on PION model.
Methods: :
PION was induced in adult Sprague-Dawley rats by illuminating the posterior portion of optic nerve with Nd:YAG laser immediately after intravenous injection of erythrosine B (EB). The integrity of the circulation in the retina and optic nerve was examined by FITC-dextran extravasation 1 hour after PION induction. The histopathologic and inflammatory changes of the optic nerve were characterized by H&E and ED1 immunostaining. RGC survival at different time points after PION induction, with or without neurotrophic application, was quantified by counting the number of Fluorogold retrograde-labeled RGCs in retina flat mounts.
Results: :
Fluorescein dye leakage was observed in the lesion area of the optic nerve one hour after PION induction. The lesion area of the optic nerve became edematous 3 days post injury and then underwent cavernous degeneration. ED1 positive microglia/macrophages first appeared in the lesion area and migrated to the distal portion of optic nerve as well as optic chiasm. RGCs died in a time dependent manner and around 30% RGCs survived 3 weeks post injury. Multiple application of BDNF or CNTF, however, could rescue RGC survival up to 70% 3 weeks post injury.
Conclusions: :
The retinal and optic nerve changes occurring after PION induction were similar to key features of human PION. Our model provides a novel platform for future research on detailed pathogenesis and molecular changes in PION; and can be further optimized for pre-clinical drug screening of interventional agents against PION as well as other CNS ischemic disease.
Keywords: ischemia • apoptosis/cell death • neuroprotection