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G. Chidlow, J. P. M. Wood, R. J. Casson; Optic Nerve and Retinal Changes Following Chronic Occlusion of the Bilateral Common Carotid Arteries in Rats. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4503.
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Analysis of the myriad effects of ischemia on the retina and optic nerve in rodents has, in the main, been explored using acute models of ischemia. Acute ischemia can be induced by elevation of intraocular pressure above systolic blood pressure or via temporary ligation of the central retinal artery. Acute ischemic episodes are, however, less common clinically than chronic hypoxia/ischemia. Recent work has documented that prolonged reduction of blood flow by occlusion of the bilateral common carotid arteries (BCCAO) leads to retinal degeneration. As such, the procedure may be a valid model for investigating neuroprotective strategies for ischemic diseases. The aim of the current work was, firstly, to confirm these recent findings, and secondly, to explore the effect of BCCAO on neuronal, glial, axonal and structural elements of the optic nerve, optic nerve head and retina.
Adult Sprague-Dawley rats were anaesthetised and a ventral incision was made. The common carotid arteries were then bilaterally separated from the carotid sheath and vagus nerve. The arteries were ligated with silk sutures. Sham animals received the same operation without occlusion of the vessels. Rats were killed at various time points following the procedure. For immunohistochemistry experiments, eyes and optic nerves were enucleated, fixed in buffered formalin, embedded in paraffin and 5µm thick sections were taken. Sections were then processed for immunohistochemistry using standard methodologies. For Real-time and conventional RT-PCR and Western blotting experiments, rats were killed by rising CO2, retinas and optic nerves were taken immediately and processed using standard methodologies.
BCCAO resulted in a time-dependent death of retinal ganglion cell (RGC) bodies and an accompanying degeneration of the axons that form the optic nerve. This was apparent from histological observation, reductions in the mRNAs of RGC markers, and decreased levels of RGC-specific proteins, such as neurofilaments, Thy1, Brn-3 and ß-tubulin. BCCAO also caused changes to markers of other retinal cell types, including Müller cells, microglia, horizontal cells, amacrine cells, and to components of the optic nerve head.
BCCAO represents a valid and relevant chronic model for investigating the effects of ischemia on the retina and optic nerve. Both acute and delayed changes were evident in the retina and optic nerve after BCCAO, indicating that there are multiple points of intervention available for targeting by potential neuroprotective strategies.
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