title: Protective effects of remote ischemic conditioning against ischemia/reperfusion-induced retinal injury in rats.
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.
authors.affiliation: Department of Ophthalmology,Xuanwu Hospital,Capital Medical University,Beijing,China.
authors.forename: Xuxiang
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Brownell-Talbot School,Omaha,Nebraska.
authors.forename: Yunneng
authors.initials: Y
authors.lastname: Jizhang
authors.affiliation: Department of Ophthalmology,Xuanwu Hospital,Capital Medical University,Beijing,China.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Neurosurgery,Wayne State University School of Medicine,Detroit,Michigan.
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Kwiecien
authors.affiliation: Institute of Hypoxia Medicine,Xuanwu Hospital,Capital Medical University,Beijing,China.
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.affiliation: Institute of Hypoxia Medicine,Xuanwu Hospital,Capital Medical University,Beijing,China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery,Xuanwu Hospital,Capital Medical University,Beijing,China.
authors.forename: Xunming
authors.initials: X
authors.lastname: Ji
authors.affiliation: Department of Ophthalmology,Xuanwu Hospital,Capital Medical University,Beijing,China.
authors.forename: Changhong
authors.initials: C
authors.lastname: Ren
authors.affiliation: Department of Neurosurgery,Wayne State University School of Medicine,Detroit,Michigan.
authors.forename: Yuchuan
authors.initials: Y
authors.lastname: Ding
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000150:complications*; D019194:Ischemic Preconditioning / Q000379:methods*; D008297:Male; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000209:etiology* / Q000517:prevention & control*; D012164:Retinal Diseases / Q000209:etiology* / Q000517:prevention & control*; D013997:Time Factors
chemical_list: D005904:Glial Fibrillary Acidic Protein; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D051547:Heme Oxygenase-1