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M. C. Holman, G. Chidlow, J. P. M. Wood, R. J. Casson; Hyperglycaemic Protects Against Chronic Hypoperfusion of the Optic Nerve and Retina. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4053.
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It is well accepted that glucose worsens ischemic injury in the brain, however studies have indicated that elevated vitreal glucose levels can potently attenuate acute ischemic retinal damage. Whether this remarkable protective effect could persist in a more prolonged ischemic insult was hitherto unknown. Here, we have assessed the effect of hyperglycaemia on chronic vascular hypoperfusion-related optic neuropathy and retinopathy with a rat model imitating normal tension glaucoma.
Adult Sprague-Dawley rats were divided in to four groups: Hypergylcaemic and normoglycaemic shams and hyperglycaemic and normoglycaemic two vessel occlusion (2VO). Hyperglycaemia was achieved by pancreatic insult with a single injection of Streptozotocin. Rats were anaesthetised and the common carotid arteries were permanently ligated with silk sutures. Sham animals received the same operation without ligation of the vessels. Rats were killed at one week by saline perfusion and the eyes removed for processing. 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 RT-PCR and Western blotting experiments, retinas and optic nerves were taken immediately following saline perfusion and processed using standard methodologies.
Both the hyperglycaemic and normoglycaemic sham groups showed no retinal or optic nerve damage on any mode of testing. Normoglycaemic 2VO animals showed drastic loss of ganglion and horizontal cells, and marked activation of all glial cells. Hyperglycemic 2VO animals showed less damage comparred to normoglycaemic 2VO animals by all measures. They showed less glial activation and more neurofilament on immunohistochemistry. This data was significant and correlated with real time RT-PCR and western blotting techniques.
2VO represents a robust model for chronic hypoperfusion in the rat, and imitates that of normal tension glaucoma. Our study has found that hyperglycaemia has a remarkable ability to significantly attenuate ischemic injury to the retina and optic nerve. This exciting result indicates potential new information and therapies for conditions such as glaucoma. The mechanism by which hyperglycaemia affects this however, is unknown, and represents an avenue for further neuroprotection research.
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