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C. Stowell, L. Wang, J. Lan, C. F. Burgoyne, G. A. Cioffi, A. Zhou; The Role of CPE in Ischemic-Tolerant Retinas. Invest. Ophthalmol. Vis. Sci. 2008;49(13):773.
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Carboxypeptidase E (CPE) is an exopeptidase that mediates the biosynthesis of neuropeptides in the brain. The expression of CPE has been shown to be up-regulated in ischemic rat brains, and CPE knockout mice have been shown to be more susceptible to ischemic brain injury. It has been proposed, that in the brain CPE may play a neuroprotective role against ischemic injury. A detectable expression and a robust response of this protease to light stimulus have been reported for the rat retina. It is not known whether or not CPE may be involved in the retina’s response to ischemic stress and if so what role(s) CPE has in the response. The objectives of this study were to validate an ischemic-tolerant model in the rat retina, and determine the role of CPE in the tolerant retinas.
Injurious retinal ischemia was induced by increasing the intraocular pressure (IOP) to 110 mmHg for 60 minutes in anesthetized Sprague-Dawley rats. An increase in IOP to 110 mmHg for 8 minutes constituted the preconditioning stimulus. The tolerance was induced by preconditioning the retina 48 hours prior to the 60-minute ischemia. Sham-treated retinas were used as a control. Retinal sections were prepared 24 hours after ischemia and examined with Fluoro-Jade B staining, TUNEL staining and immunocytochemistry (ICC) of CPE.
Both Fluoro-Jade B and TUNEL staining showed a decrease in cell injury in the retinas that were treated with the preconditioning ischemia followed by the injurious ischemia, when compared to the extent of cell injury in retinas treated with injurious ischemia alone. ICC analyses of CPE showed that there was a robust increase in its expression in both the pre-conditioned and the tolerant retinas when compared to the sham retinas.
The ischemic-tolerant paradigm we are using is a valid model for producing tolerance in the retina. The increase in CPE expression in the pre-conditioned as well as tolerant retinas suggests a neuroprotective role for CPE in the retina. The spatial and temporal changes of CPE under preconditioned, ischemic and ischemic-tolerant conditions in the retina remain to be established.
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