Abstract
Purpose: :
The development of fundus imaging techniques has revolutionized our ability to monitor in vivo retinal changes in animal models of optic neuropathies. We used various non-invasive imaging modalities to delineate the acute and chronic anatomical changes in experimental anterior ischemic optic neuropathy (AION).
Methods: :
We induced photochemical thrombosis model of AION in adult mice. We used Spectralis (Heidelberg) to perform fluorescein angiography, spectral-domain optical coherence tomography (SD-OCT), and fundus imaging of wild-type and transgenic Thy1-YFP mice, which expressed YFP (green) fluorescence in about 20 retinal ganglion cells (RGCs), over days to weeks following experimental AION.
Results: :
Immediately following AION, fluorescein angiography showed transient leakage at the optic nerve head and impaired retinal perfusion. Autofluorescence imaging of the Thy1-YFP mice yielded high resolution views of the RGC cell bodies, dendrites and axons. Within one-hour after AION, there was disruption of the YFP protein expression, and within days, retrograde degeneration of the RGC axons. These images were comparable to microscopy of whole mount retinal and optic nerve preparations, which also showed anterograde degeneration of the RGC axons. Using SD-OCT to assess post-AION retinal changes, we found acute swelling of the inner retina (RNFL + RGC + IPL layers) (AION eyes: 108.8 ± 3.8 µm, control eyes: 79.2 ± 0.6 µm, p < 0.000001) at day-1 compared to baseline. This swelling resolved by week-1. At weeks 2 to 3, the AION eyes showed progressive thinning of the inner retina (at week-3, AION eyes: 68.2 ± 0.9 µm, control eyes: 75.6 ± 0.7 µm, p < 0.000001), which remained unchanged at week-6 (AION eyes: 67.0 ± 1.0 µm, control eyes: 76.2 0 ± 0.8 µm, p < 0.000001).
Conclusions: :
We utilized non-invasive imaging techniques to quantify important changes following experimental AION, which can be used as outcome measures in future testing of potential therapies.
Keywords: optic nerve • ischemia • imaging methods (CT, FA, ICG, MRI, OCT, RTA, SLO, ultrasound)