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Abstract #3453 Published in IGR 4-2
Mouse models of retinal ischemic tolerance
Zhu Y; Ohlemiller KK; McMahan BK; Gidday JMInvestigative Ophthalmology and Visual Science 2002; 43: 1903-1911
PURPOSE: A brief period of noninjurious retinal ischemia, termed preconditioning, has been documented in rats to afford transient protection from retinal ischemic injury, a phenomenon known as ischemic tolerance. The present study was undertaken to develop and systematically characterize mouse models of ischemic tolerance. METHODS: Retinal ischemic injury was caused by elevating intraocular pressure for 30, 45, or 60 minutes in chloral hydrateBanesthetized ND4 Swiss-Webster mice. Random animals were preconditioned 24 hours earlier with either five minutes of retinal ischemia or by exposing conscious animals to hypoxia (11% oxygen) for two hours. Flash electroretinograms were recorded one day and one week after ischemia. At one or four weeks after ischemia, eyes were perfusion fixed for microscopic examination and quantification of layer thickness and cell counts. RESULTS: Retinal ischemia resulted in significant, duration-dependent reductions in inner retinal layer thickness and cell loss in the inner nuclear and ganglion cell layers. A duration-dependent attenuation in a- and b-wave amplitudes was concomitantly noted. The ischemic and hypoxic preconditioning treatments significantly attenuated the ischemia-induced changes in retinal morphology and function, even after four weeks of recovery. Tolerance was observed at 24 hours after ischemic preconditioning, but not at 72 hours. CONCLUSIONS: Two models of retinal ischemic tolerance are presented wherein ischemic or hypoxic preconditioning afforded morphological and functional evidence of protection from retinal ischemic injury in mice. These two murine models should be useful for studies in mutant mice to elucidate endogenous genetic and molecular mechanisms of retinal protection that may then be used to design treatments for ischemic retinopathies.
Dr. Y. Zhu, Department of Neurosurgery, Washington University School of Medicine, St Louis, MO, USA
Classification:
5 Experimental glaucoma; animal models
11.9 Gene therapy (Part of: 11 Medical treatment)
