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N. Yonemura, A. Hirata, Y. Inomata, T. Koga, M. Honjo, H. Tanihara; Neuroprotective Effect of Rho-Associated Protein Kinase Inhibitor, Y-27632, in the Eye . Invest. Ophthalmol. Vis. Sci. 2003;44(13):5231.
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Purpose:To investigate whether Rho-associated protein kinase inhibitor, Y-27632, has neuroprotective effects against ischemic retinal injury in rat eyes. Methods:Experiments were performed in SD rat (male, 6 weeks of age). The retinal ischemia was induced by increase of the intraocular pressure to 130mmHg for 45min.Y-27632 solution (0.1, 1 and 10 mM / 5µl) or PBS (5µl) for control was injected into vitreous space prior to induction of retinal ischemia. Seven days later, each eye was enucleated and analyzed morphometrically, including counting the number of retinal ganglion cells (RGCs) and measuring the thickness of the inner plexiform layers (IPL). Differences were analyzed by paired t-test. Retinal damage was assessed by TUNEL method 18 hours after induction of retinal ischemia. Results:In control eyes, the number of RGCs and the thickness of IPL were reduced significantly as against normal eyes (RGCs: 51.67±5.59 vs. 38.94 ± 3.26 cells/mm p=0.013, IPL: 34.04 ± 2.29 vs. 18.93 ± 3.29µm p<0.001). In eyes pretreated with Y-27632 (10mM), these were retained significantly as compared with the control eyes (RGCs: 48.11±4.96 vs. 38.94 ± 3.26 cells/mm p=0.01, IPL: 28.6±3.26 vs. 18.93 ± 3.29µm p<0.001). However, statistically significant differences were not found at lower concentration of Y-27632. In control eyes, TUNEL positive cells were observed in the ganglion cell layer and the inner nuclear layer. In contrast, pretreatment with Y-27632 (10mM) provided decrease of the TUNEL positive cells in both layers. Conclusions: Rho-associated protein kinase inhibitor, Y-27632, may be useful in preventing retinal cell death by ischemic injury in rat eyes.
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