Abstract
Purpose: :
Anterior ischemic optic neuropathy (AION) is due to ischemia of the optic nerve head, leading to significant vision loss. Our goal was to study the early changes following optic nerve head ischemia and to test the efficacy of a potential therapy in experimental AION.
Methods: :
We used a photochemical thrombosis model of AION in mouse, with laser-directed optic nerve head ischemia in the presence of rose bengal. Intracranial flash visual evoked potential (fVEP) recordings and histological methods were utilized.
Results: :
Within days after experimental AION, there was significant optic nerve head swelling, vascular leakage, and selective loss of the peri-papillary microvasculature. Consistent with these ischemic changes, there was functional impairment as demonstrated by a decrease in the amplitude of fVEP responses. Coincident with these histological and functional deteriorations, there were signs of inflammatory cellular reactions, with up-regulation of macro- and microglia. Interestingly, the expression of -B crystallin (BC), a small heat shock protein abundant in the lens of the eye, was significantly increased in the optic nerve head and retina at day one following experimental AION. This led us to test BC as a potential treatment in experimental AION. Injected daily for 3 days following optic nerve head ischemia, BC did not dampen post-ischemic macro- and microglial responses in wild-type or in BC knock-out mice. Since significant retinal ganglion cell loss occurs within the first 3 weeks following experimental AION, leading to irreversible vision loss, we tested the effects of a 3-week course of BC, with weekly fVEP measurements to monitor visual function. After 3 weeks of BC treatment, there was a significant improvement of the fVEP latencies in the BC-treated group but not in the saline-treated group, without an improvement in the fVEP amplitudes or the number of surviving retinal ganglion cells.
Conclusions: :
BC, an important chaperone and key molecule in inflammation and neurodegeneration, was acutely up-regulated in experimental AION. Short-term BC treatment immediately following optic nerve head ischemia did not have significant effects, while a 3-week course of BC injections led to a dramatic improvement of the visual pathway signal transmission, consistent with a mechanism of axonal protection.
Keywords: neuro-ophthalmology: optic nerve • ischemia • laser