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M. V. Kyhn, J. F. Kiilgaard, M. Young, H. Klassen, E. Lavik, E. Scherfig, K. Warfvinge, M. la Cour; Neuroprotection of Ischemic Injury in Pig Retina, Part I: The Injury Model. Invest. Ophthalmol. Vis. Sci. 2007;48(13):566.
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To establish and functionally characterize a porcine model of transient controlled reduced ocular perfusion pressure (OPP) resulting in acute retinal ischemia
Acute retinal ischemia was induced in 12 pigs. A needle placed in the anterior chamber connected to a fluid container and a transducer controlled and monitored the IOP. A transducer in the aorta monitored the mean arterial blood pressure. OPP's of 30, 20, 10, 5 & 0 mmHg (n=5) were obtained, and kept at a constant level for 2 hours. Evaluation with a slow-stimulation sequence mfERG-protocol was performed at day 14. mfERG was also recorded in 7 pigs at day 0, 3, 14, 28 and 42 after 5 mmHg OPP. Eyes were enucleated for histological evaluation. The thicknesses of the outer nuclear layer (ONL) and the inner plexiform layer (IPL) were measured.
The model transiently elevated IOP resulting in a reduced OPP. Induced mfERG responses were evaluated. A negative amplitude deflection at 50 ms (iN1,) was the most consistent finding. Electrophysiological evaluation 14 days after OPP of 30 and 20 mmHg showed unaffected iN1 amplitude. At OPP of 10 and 5 mmHg the iN1 amplitudes were reduced to 38%-43%, respectively. At 0 mmHg of OPP no retinal response could be detected. In the 7 pigs with 5 mmHg OPP a significant amplitude reduction was found in the treated eyes, compared to the contra-lateral untreated eye (p<0.0003). In histological specimens the ONL thickness was normal, whereas the IPL was thinned.
We have established a method by which the OPP can be kept at a constant and controlled level for a limited period of time. OPP of 5 mmHg caused a significant reduction in the induced mfERG-component amplitude. Significant damage of the inner retinal structures, evaluated by IPL-thickness, was noted, while the outer retinal layers, evaluated by ONL-thickness remained unaffected. Low OPP of 5 mmHg over 2 hours induced measurable changes in the slow-stimulation mfERG. We have used this method to investigate neuroprotection against ganglion cell loss after reduced OPP, as presented in part II and III.
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