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Protective effects of remote ischemic conditioning against ischemia/reperfusion-induced retinal injury in rats

Published online by Cambridge University Press:  15 April 2014

XUXIANG ZHANG ,
YUNNENG JIZHANG ,
XIAOYING XU ,
TIMOTHY D. KWIECIEN ,
NING LI ,
YING ZHANG ,
XUNMING JI ,
CHANGHONG REN  and
YUCHUAN DING
XUXIANG ZHANG
Affiliation:
Department of Ophthalmology, Xuanwu Hospital, Capital Medical University, Beijing, China
YUNNENG JIZHANG
Affiliation:
Brownell-Talbot School, Omaha, Nebraska Institute of Hypoxia Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China
XIAOYING XU*
Affiliation:
Department of Ophthalmology, Xuanwu Hospital, Capital Medical University, Beijing, China
TIMOTHY D. KWIECIEN
Affiliation:
Department of Neurosurgery, Wayne State University School of Medicine, Detroit, Michigan
NING LI*
Affiliation:
Institute of Hypoxia Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China
YING ZHANG
Affiliation:
Institute of Hypoxia Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China
XUNMING JI*
Affiliation:
Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China
CHANGHONG REN*
Affiliation:
Department of Ophthalmology, Xuanwu Hospital, Capital Medical University, Beijing, China Institute of Hypoxia Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China
YUCHUAN DING
Affiliation:
Department of Neurosurgery, Wayne State University School of Medicine, Detroit, Michigan
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Abstract

Limb remote ischemic conditioning (LRIC) provides a physiologic strategy for harnessing the body’s endogenous protective capabilities against injury induced by ischemia–reperfusion in the central nervous system. The aim of the present study was to determine if LRIC played a role in protecting the retina from ischemia–reperfusion injury. A total of 81 adult male Sprague-Dawley rats were randomly assigned to sham and ischemia/reperfusion with or without remote LRIC arms. The retinal ischemic model was generated through right middle cerebral artery occlusion (MCAO) and pterygopalatine artery occlusion for 60 min followed by 1, 3, and 7 days of subsequent reperfusion. LRIC was conducted immediately following MCAO by tightening a tourniquet around the upper thigh and releasing for three cycles. Paraffin sections were stained with hematoxylin and eosin in order to quantify the number of cells in retinal ganglion cells (RGCs) layer throughout the duration of the study. Cellular expression of glial fibrillary acidic protein (GFAP) was detected and examined through immunohistochemistry. Protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) was also analyzed by Western blot techniques. Our study demonstrated that the loss of cells in RGC layer was attenuated by LRIC treatment at 3 and 7 days following reperfusion (P < 0.05). Immunohistochemistry studies depicted a gradual increase (P < 0.05) in GFAP levels from day 1 through day 7 following ischemia and subsequent reperfusion, whereas LRIC reduced GFAP levels at 1, 3, and 7 days postreperfusion. In addition, LRIC increased the expression of Nrf2 and HO-1 at day 1 and 3 following ischemia/reperfusion. This particular study is the first remote conditioning study applicable to retinal ischemia. Our results strongly support the position that LRIC may be used as a noninvasive neuroprotective strategy, which provides retinal protection from ischemia–reperfusion injury through the upregulation of antioxidative stress proteins, such as Nrf2 and HO-1.

Keywords

Retinal injuryRemote ischemic conditioningGlial fibrillary acidic proteinNuclear factor erythroid 2-related factor 2Heme oxygenase-1
Type
Research Articles
Information
Visual Neuroscience , Volume 31 , Issue 3 , May 2014 , pp. 245 - 252
Copyright
Copyright © Cambridge University Press 2014 

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References

Arai-Gaun, S., Katai, N., Kikuchi, T., Kurokawa, T., Ohta, K. & Yoshimura, N. (2004). Heme oxygenase-1 induced in muller cells plays a protective role in retinal ischemia-reperfusion injury in rats. Investigative Ophthalmology & Visual Science 45, 4226–4232.Google Scholar
Block, F., Grommes, C., Kosinski, C., Schmidt, W. & Schwarz, M. (1997). Retinal ischemia induced by the intraluminal suture method in rats. Neuroscience Letters 232, 45–48.Google Scholar
Botker, H.E., Kharbanda, R., Schmidt, M.R., Bottcher, M., Kaltoft, A.K., Terkelsen, C.J., Munk, K., Andersen, N.H., Hansen, T.M., Trautner, S., Lassen, J.F., Christiansen, E.H., Krusell, L.R., Kristensen, S.D., Thuesen, L., Nielsen, S.S., Rehling, M., Sorensen, H.T., Redington, A.N. & Nielsen, T.T. (2010). Remote ischaemic conditioning before hospital admission, as a complement to angioplasty, and effect on myocardial salvage in patients with acute myocardial infarction: a randomised trial. Lancet 375, 727–734.Google Scholar
Dreixler, J.C., Bratton, A., Du, E., Shaikh, A.R., Savoie, B., Alexander, M., Marcet, M.M & Roth, S. (2011 a). Mitogen-activated protein kinase phosphatase-1 (MKP-1) in retinal ischemic preconditioning. Experimental Eye Research 93, 340–349.Google Scholar
Dreixler, J.C., Sampat, A., Shaikh, A.R., Alexander, M., Marcet, M.M & Roth, S. (2011 b). Protein kinase B (Akt) and mitogen-activated protein kinase p38alpha in retinal ischemic post-conditioning. Journal of Molecular Neuroscience 45, 309–320.Google Scholar
Eng, L.F., Ghirnikar, R.S. & Lee, Y.L. (2000). Glial fibrillary acidic protein: GFAP-thirty-one years (1969-2000). Neurochemical Research 25, 1439–1451.Google Scholar
Fernandez, D.C., Bordone, M.P., Chianelli, M.S. & Rosenstein, R.E. (2009 a). Retinal neuroprotection against ischemia-reperfusion damage induced by postconditioning. Investigative Ophthalmology & Visual Science 50, 3922–3930.Google Scholar
Fernandez, D.C., Chianelli, M.S. & Rosenstein, R.E. (2009 b). Involvement of glutamate in retinal protection against ischemia/reperfusion damage induced by post-conditioning. Journal of Neurochemistry 111, 488–498.Google Scholar
Flammer, J., Orgul, S., Costa, V.P., Orzalesi, N., Krieglstein, G.K., Serra, L.M., Renard, J.P. & Stefansson, E. (2002). The impact of ocular blood flow in glaucoma. Progress in Retinal and Eye Research 21, 359–393.Google Scholar
Hausenloy, D.J. & Yellon, D.M. (2008). Remote ischaemic preconditioning: Underlying mechanisms and clinical application. Cardiovascular Research 79, 377–386.Google Scholar
Hausenloy, D.J. & Yellon, D.M. (2011). The therapeutic potential of ischemic conditioning: An update. Nature Reviews Cardiology 8, 619–629.Google Scholar
He, M., Pan, H., Chang, R.C., So, K.F., Brecha, N.C. & Pu, M. (2014). Activation of the Nrf2/HO-1 antioxidant pathway contributes to the protective effects of Lycium barbarum polysaccharides in the rodent retina after ischemia-reperfusion-induced damage. PLoS One 9, e84800.Google Scholar
Hoda, M.N., Siddiqui, S., Herberg, S., Periyasamy-Thandavan, S., Bhatia, K., Hafez, S.S., Johnson, M.H., Hill, W.D., Ergul, A., Fagan, S.C. & Hess, D.C. (2012). Remote ischemic perconditioning is effective alone and in combination with intravenous tissue-type plasminogen activator in murine model of embolic stroke. Stroke 43, 2794–2799.Google Scholar
Jadhav, A.P., Roesch, K. & Cepko, C.L. (2009). Development and neurogenic potential of Muller glial cells in the vertebrate retina. Progress in Retinal and Eye Research 28, 249–262.Google Scholar
Lai, I.R., Chang, K.J., Chen, C.F. & Tsai, H.W. (2006). Transient limb ischemia induces remote preconditioning in liver among rats: The protective role of heme oxygenase-1. Transplantation 81, 1311–1317.Google Scholar
Lee, J.M., Calkins, M.J., Chan, K., Kan, Y.W. & Johnson, J.A. (2003). Identification of the NF-E2-related factor-2-dependent genes conferring protection against oxidative stress in primary cortical astrocytes using oligonucleotide microarray analysis. The Journal of Biological Chemistry 278, 12029–12038.Google Scholar
Li, S.Y., Fu, Z.J. & Lo, A.C. (2012). Hypoxia-induced oxidative stress in ischemic retinopathy. Oxidative Medicine and Cellular Longevity 2012, 426769.Google Scholar
Meng, R., Asmaro, K., Meng, L., Liu, Y., Ma, C., Xi, C., Li, G., Ren, C., Luo, Y., Ling, F., Jia, J., Hua, Y., Wang, X., Ding, Y., Lo, E.H. & Ji, X. (2012). Upper limb ischemic preconditioning prevents recurrent stroke in intracranial arterial stenosis. Neurology 79, 1853–1861.Google Scholar
Moi, P., Chan, K., Asunis, I., Cao, A. & Kan, Y.W. (1994). Isolation of NF-E2-related factor 2 (Nrf2), a NF-E2-like basic leucine zipper transcriptional activator that binds to the tandem NF-E2/AP1 repeat of the beta-globin locus control region. Proceedings of the National Academy of Sciences of the United States of America 91, 9926–9930.Google Scholar
Obolensky, A., Berenshtein, E., Konijn, A.M., Banin, E. & Chevion, M. (2008). Ischemic preconditioning of the rat retina: Protective role of ferritin. Free Radical Biology & Medicine 44, 1286–1294.Google Scholar
Osborne, N.N., Block, F. & Sontag, K.H. (1991). Reduction of ocular blood flow results in glial fibrillary acidic protein (GFAP) expression in rat retinal Muller cells. Visual Neuroscience 7, 637–639.Google Scholar
Osborne, N.N., Casson, R.J., Wood, J.P., Chidlow, G., Graham, M. & Melena, J. (2004). Retinal ischemia: Mechanisms of damage and potential therapeutic strategies. Progress in Retinal and Eye Research 23, 91–147.Google Scholar
Owuor, E.D. & Kong, A.N. (2002). Antioxidants and oxidants regulated signal transduction pathways. Biochemical Pharmacology 64, 765–770.Google Scholar
Ren, C., Gao, M., Dornbos, D. 3rd, Ding, Y., Zeng, X., Luo, Y. & Ji, X. (2012). Remote ischemic post-conditioning reduced brain damage in experimental ischemia/reperfusion injury. Neurological Research 33, 514–519.Google Scholar
Satoh, T., Okamoto, S.I., Cui, J., Watanabe, Y., Furuta, K., Suzuki, M., Tohyama, K. & Lipton, S.A. (2006). Activation of the Keap1/Nrf2 pathway for neuroprotection by electrophilic [correction of electrophilic] phase II inducers. Proceedings of the National Academy of Sciences of the United States of America 103, 768–773.Google Scholar
Saxena, P., Newman, M.A., Shehatha, J.S., Redington, A.N. & Konstantinov, I.E. (2010). Remote ischemic conditioning: Evolution of the concept, mechanisms, and clinical application. Journal of Cardiac Surgery 25, 127–134.Google Scholar
Shah, Z.A., Li, R., Thimmulappa, R.K., Kensler, T.W., Yamamoto, M., Biswal, S. & Dore, S. (2007). Role of reactive oxygen species in modulation of Nrf2 following ischemic reperfusion injury. Neuroscience 147, 53–59.Google Scholar
Shelton, P. & Jaiswal, A.K. (2013). The transcription factor NF-E2-related factor 2 (Nrf2): A protooncogene? FASEB Journal 27, 414–423.Google Scholar
Shokeir, A.A., Hussein, A.M., Barakat, N., Abdelaziz, A., Elgarba, M. & Awadalla, A. (2014). Activation of nuclear factor erythroid 2-related factor 2 (Nrf2) and Nrf-2-dependent genes by ischaemic pre-conditioning and post-conditioning: New adaptive endogenous protective responses against renal ischaemia/reperfusion injury. Acta Physiologica (Oxford). 210, 342–353.Google Scholar
Veighey, K. & Macallister, R.J. (2012). Clinical applications of remote ischemic preconditioning. Cardiology Research and Practice 2012, 620681.Google Scholar
Verma, D. (1993). Pathogenesis of diabetic retinopathy – The missing link? Medical Hypotheses 41, 205–210.Google Scholar
Wei, M., Xin, P., Li, S., Tao, J., Li, Y., Li, J., Liu, M., Zhu, W. & Redington, A.N. (2011). Repeated remote ischemic postconditioning protects against adverse left ventricular remodeling and improves survival in a rat model of myocardial infarction. Circulation Research 108, 1220–1225.Google Scholar
Zhang, C., Rosenbaum, D.M., Shaikh, A.R., Li, Q., Rosenbaum, P.S., Pelham, D.J. & Roth, S. (2002). Ischemic preconditioning attenuates apoptotic cell death in the rat retina. Investigative Ophthalmology & Visual Science 43, 3059–3066.Google Scholar
Zhao, H. (2009). Ischemic postconditioning as a novel avenue to protect against brain injury after stroke. Journal of Cerebral Blood Flow and Metabolism 29, 873–885.Google Scholar
Zhao, J., Kobori, N., Aronowski, J. & Dash, P.K. (2006). Sulforaphane reduces infarct volume following focal cerebral ischemia in rodents. Neuroscience Letters 393, 108–112.Google Scholar
Zhao, Z.Q. & Vinten-Johansen, J. (2006). Postconditioning: Reduction of reperfusion-induced injury. Cardiovascular Research 70, 200–211.Google Scholar
Zhu, Y., Zhang, Y., Ojwang, B.A., Brantley, M.A. Jr. & Gidday, J.M. (2007). Long-term tolerance to retinal ischemia by repetitive hypoxic preconditioning: Role of HIF-1alpha and heme oxygenase-1. Investigative Ophthalmology & Visual Science 48, 1735–1743.Google Scholar