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Y Zhu, BK McMahan, JM Gidday; Chemical Preconditioning Against Retinal Ischemic Injury in the Mouse with Cobalt Chloride . Invest. Ophthalmol. Vis. Sci. 2002;43(13):3312.
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Purpose: Our recent studies (Zhu et al., IOVS, submitted) have elucidated the ability of brief ischemia or systemic hypoxia to promote a state of ischemic tolerance in retina. The present study was undertaken to determine if the retina could be chemically preconditioned with similarly robust neuroprotection. Methods: Adult male Swiss-Webster ND4 mice were subjected to 30-min retinal ischemia by IOP elevation to 90 mmHg; this duration of ischemia leads to a moderate degree of retinal injury in this strain. 24 h prior to this insult, half the animals were injected with cobalt chloride (60 mg/kg, ip); other groups of mice received cobalt chloride without subsequent ischemia (n=3), or served as untreated, nonischemic controls (n=11). One week postischemia, animals were transcardiac perfused with paraformaldehyde, retinas paraffin-embedded, and 5-µm sections were stained with H&E for histopathologic analyses. Results: Thicknesses of the inner retinal layers (OLM-ILM, INL, IPL) as well as cell counts in the INL and GCL were significantly (Wilcoxen signed rank test) and robustly preserved in ischemic retinae from animals receiving cobalt chloride (n=5) relative to ischemic retinae from untreated mice (n=7); cobalt chloride alone caused no adverse cellular effects in nonischemic eyes. Conclusion: A state of ischemic tolerance can be induced in retina following cobalt chloride preconditioning. This noninvasive model of ischemic tolerance will be useful to examine the mechanistic basis for this neuroprotection vis-à-vis hypoxic or ischemic preconditioning. We are exploring whether cobalt chloride serves to upregulate particular stress proteins and/or activates the hypoxia-inducible transcription factor called HIF-1α, which promotes the expression of a variety of genes whose products would increase the tissue's resistance to an ischemic stress.
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