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B. Gesslein, L. Gustafsson, R. Carpio, M. Malmsjo; Involvement of Mitogen-Activated Protein Kinases in the Porcine Retinal Arteries and Neuroretina Following Retinal Ischemia-Reperfusion Injury. Invest. Ophthalmol. Vis. Sci. 2008;49(13):6120. doi: https://doi.org/.
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Identification of intracellular transduction pathways that are activated in ischemia related conditions of the eye may be important in order to find pharmacological targets to prevent retinal injury. So far, most studies have focused on identifying neuroprotective agents. The retinal blood vessels are key organs in circulatory failure and this study was therefore designed to examine the retinal vasculature separately from the neuroretina. Mitogen-activated protein kinases (MAPKs), consisting of three major enzymes: extracellular signal-regulated kinase (ERK), p38, and c-jun N-terminal kinase (JNK). The regulation of MAPKs has been implicated in cerebral and cardiac ischemia and studies on MAPKs and retinal ischemia have started to emerge. Nevertheless, knowledge about the role for MAPKs in retinal ischemia is still limited. Our aim was to examine ERK1/2, p38 and JNK in a novel porcine model of pressure induced ischemia and reperfusion.
Retinal ischemia was induced by elevating the intraocular pressure in porcine eyes for 1 hour, followed by 5, 12, or 20 hours of reperfusion. ERK1/2, p38 and JNK mRNA levels was quantified using real-time PCR. Phosphorylated ERK1/2, p38 and JNK protein levels and localization was studied using Western blot and immunofluorescence staining techniques. The neuroretina and retinal arteries were studied separately.
Results from the real-time PCR and western blot experiments show alterations in the MAPK mRNA and protein expression in the neuroretina and retinal arteries following ischemia-reperfusion injury. ERK1/2, p38 and JNK pathway proteins can be identified by immunofluorescence staining both in the porcine retina and retinal arteries in control and ischemia reperfusion eyes.
The study was performed using porcine eyes, which has a primate like vasculature. The results show alterations of the MAPK signal-transduction pathway in the retinal vasculature following retinal circulatory failure, suggesting that the MAPKs may be of importance in the development of retinal ischemia-reperfusion injury and that they may provide new targets for pharmacological treatments.
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