Effects of aminoguanidine on retinal apoptosis in mice with oxygen-induced retinopathy
Author:
  • Article
  • | |
  • Metrics
  • |
  • Reference [17]
  • |
  • Related [20]
  • | | |
  • Comments
    Abstract:

    AIM: To explore the protective effects of aminoguanidine (AG) on retinal apoptosis in mice with oxygen-induced retinopathy (OIR).METHODS:A total of 80 C57BL/6J mice, aged 7 days, were randomly divided into four groups:normal, high oxygen, high oxygen saline and high oxygen treated with AG. In the normal group, mice were housed in normoxic conditions from postnatal day P7 to P17. Mice in the other 3 groups were placed under hyperoxic conditions (75±2%O2) in an oxygen-regulated chamber for 5 days and subsequently placed in normoxic conditions for 5 days. Mice in the AG group were treated once daily, from P12 to P17, with AG hemisulfate (100mg/kg body weight, intraperitoneally) dissolved in physiological saline. An equivalent amount of 0.9% physiological saline was administered, as above, to mice in the high oxygen saline group. Ten mice were randomly selected from each group on P14 and on P17, euthanized and the retinas examined. Apoptotic cells in the retina were detected using the terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) method. The expression of nitric oxide synthase (iNOS) in the retina was detected by immunohistochemistry and changes in rod cells were observed using electron microscopy.RESULTS:TUNEL-positive cells and iNOS immunoreactive neurons were present in the inner nuclear and ganglion cell retinal layers of mice in the high oxygen group. The number of TUNEL-positive cells was significantly greater in the high oxygen group compared with the normal group (t=-20.81, P14d <0.05; t=-15.05, P17d<0.05). However, the number of TUNEL-positive cells in the AG treatment group was significantly lower (t=-13.21, P14d<0.05; t=-6.61,P17d <0.05) compared with the high oxygen group. The expression of iNOS was significantly higher in the high oxygen group compared with the normal group (t=-21.95, P14d<0.05; t=-17.30, P17d<0.05). However, the expression of iNOS in the AG treatment group was significantly lower (t=-12.17,P14d<0.05; t=-10.30,P17d<0.05) compared with the high oxygen group. The outer segments of the rods were disorganized and short in the high oxygen group. Rod morphology appeared to be slightly improved in the AG group.CONCLUSION:AG may protect retinal neurons in OIR by inhibiting apoptosis. The mechanism may be related to iNOS.

    Reference
    1 Lomuto CC, Galina L, Brussa M, Quiroga A, Alda E, Benítez AM, Bouzas L, Dinerstein NA, Erpen N, Falbo J, Manzitti J, Marinaro S, Nieto R, Sepúlveda T, Visintín P. Epidemiology of retinopathy of prematurity in publics services from Argentina during 2008. Arch Argent Pediatr 20l0;108(1):24-30
    2 Sennlaub F, Courtois Y, Goureau O. Inducible nitric oxide synthase mediates retinal apoptosis in ischemic proliferative retinopathy. J Neuro Sci 2002;22(10):3987-3993
    3 Neufeld AH, Sawada A, Becker B. Inhibition of nitric-oxide synthase 2 by aminoguanidine provides neuroprotection of retinal ganglion cells in a rat model of chronic glaucoma. Proc Natl Acad Sci USA 1999;96(17):9944-9948
    4 Smith LE, Wesolowski E, McLellan A, Kostyk SK, D’Amato R, Sullivan R, D’Amore PA. Oxygen-induced retinopathy in the mouse. Invest Ophthalmol Vis Sci 1994;35(1):101-111
    5 Fletcher EL, Downie LE, Hatzopoulos K, Vessey KA, Ward MM, Chow CL, Pianta MJ, Vingrys AJ, Kalloniatis M, Wilkinson-Berka JL. The significance of neuronal and glial cell changes in the rat retina during oxygeninduced retinopathy. Doc Ophthalmol 2010;120(1):67-86
    6 Fulton AB, Reynaud X, Hansen RM, Lemere CA, Parker C, Williams TP. Rod photoreceptors in infant rats with a history of oxygen exposure. Invest Ophthalmol Vis Sci 1999;40(1):168-174
    7 Fulton AB, Hansen RM, Moskowitz A, Akula JD. The neurovascular retina in retinopathy of prematurity. Prog Retin Eye Res 2009;28(6):452-482
    8 Fulton AB, Hansen RM, Moskowitz A. Development of rod function in term born and former preterm subjects. Optom Vis Sci 2009;86(6):E653-658
    9 Fulton AB, Hansen RM, Petersen RA, Vanderveen DK. The rod photoreceptors in retinopathy of prematurity:an electroretinographic study. Arch Ophthalmol 2001;119(4):499-505
    10 Barnaby AM, Hansen RM, Moskowitz A, Fulton AB. Development of scotopic visual thresholds in retinopathy of prematurity. Invest Ophthalmol Vis Sci 2007;48(10):4854-4860
    11Hansen RM, Fulton AB. Background adaptation in children with a history of mild retinopathy of prematurity. Invest Ophthalmol Vis Sci 2000;41(1):320-324
    12 Akula JD, Hansen RM, Martinez-Perez ME, Fulton AB. Rod photoreceptor function predicts blood vessel abnormality in retinopathy of prematurity. Invest Ophthalmol Vis Sci 2007;48(9):4351-4359
    13 Downie LE, Pianta MJ, Vingrys AJ, Wilkinson-Ber湫?渠敊潌測愠瑆慬汥?牣慨瑥獲???椮??潥牵敲慯湮???偡敮牤椠湧慬瑩潡汬??楥??㈠っ?ち????ㄠ????????扲牭??????特愠晲浥慴湩?????敡瑳瑣????卩桺慡晴楩牯?????潲瑥瑴汩楮敯扰?????慯浦愠牰楲?????潲穩汴慹渮??敩氾湊攠牃?卭??噎楥獵桲湯敬瘠猼欯楩愾??愰椷※嘵??匨欴愩氺椴琰攴爭?刱???楲渾愊琱?倠???慮敩牥洠慌湅?????敺楯湰獯瑵敬楯湳????匠桐潩獡桮慴湡椠?告???湩桮楧扲楹瑳椠潁湊?漠晗?潬硫祩杮敳湯?椭湂摥畲捫敡搠?牌攬琠楋湡潬灬慯瑮桩祡?楩湳?前听倠?ぬ??摣敨晥楲挠楅敌渮琠?浮楧捩敯???楳??渠癴敹獰瑥?伱瀠桲瑥档慥汰浴潯汲?噩楮獨?卢捩楴??楮????の??????は?????????は??扡牣??????敥?呬??塩楮渠条?奲兡??婭桯慤潥?堠????楴?????湴瑨敹爠慯捦琠楰潲湥?扡整瑵睲敩整湹?椼乩伾匠?愠湃摯??传塎???楯湬?格礯灩漾砲椰愱?椻渵搱甸挨攱搩?爴攱琭椶渳愼汢?渾攊漱瘵愠獆捵畬汴慯牮椠穁慂琬椠潈湡?楳湥?洠楒捍攬???楳??牷捩桴??敁搬?剂敡獲??楢??休き??????????ち??????扩牮??????散?味???楴????婨桩慳潴?塲???塦椠湲来?奩兮???湴摨畹挠楯扦氠数?湥業瑡牴極捲?潴硹椮搠攼?猾祄湯瑣栠慏獰敨?浨敡摬業慯瑬攠猼?桩社瀲漰砰椵愻?椱渱搨由挩攺搷?栱礳瀼潢硲椾愊?椶渠摎畡捲楡批污敮?普愠捓瑐漬爠???慡汮灰桲慡?慩捤琠楊瘬愠瑓楡潵湬?慁測搠?癵愠獚挬甠汓慴物?敬渠摁漠瑃桡敬汤楷慥汬?朠牒潗眬琠桃?晬慤捷瑥潬牬?敒硂瀮爠敁獲獧楩潮湡?楥渠′漠硤祥杬敥湴?楯湮搠畲捥敤摵?牥敳琠楮湥潵灲慯琭桧祬???椠?偮慪瑵桲潹戠楡潮汤漠杩祭??楯????ひ????????????????扩牮??㈠??婤桥慬渠杯?儠??婴桩慮湯杰?????畯慦渠?奲??婡桴慵湲杩?卹??娼桩甾????堠畏??吠??坩愾渲朰????匨男瀩瀺牥攲猲猴椶漰渼?潲显?爱攷琠楂湯慮汦?湣敯漠癅愬猠捋畲污慩牮楣稠慄琬椠潁湮?扡祲?瑲桯敮?椠乍伬匠?楩湣桯楴扥楲瑡漠牐?愠浌楩湰潴杯畮愠湓楁搮椠湁数?楰湴?浳楩捳攠?潮晤?潮硥祣杲敯湳?楳渺摴畷捯攠摤?牳整瑩楮湣潴瀠慥瑶桥祮???楩??牵慣敥晤攬猠??牳捰桥??汩楶湥??砬瀠?佹瀠桭瑩桬慤氠浡潮汤??楮???びづ?????????????????扥牴?yl-D-aspartate or nitrie oxide/superoxide in cortical cell cultures. Proc Natl Acad Sci USA 1995;92(16):7162-7166
    18 Neufeld AH, Kawai Si, Das S, Vora S, Gachie E, Connor JR, Manning PT. Loss of retinal ganglion cells following retinal ischemia:the role of inducible nitric oxide synthase. Exp Eye Res 2002;75(5):521-528
    19 Sakamoto K, Yonoki Y, Kubota Y, Kuwagata M, Saito M, Nakahara T, Ishii K. Inducible nitric oxide synthase inhibitors abolished histological protection by late ischemic preconditioning in rat retina. Exp Eye Res 2006;82(3):512-518
    20 Yaylak F, Canbaz H, Caglikulekci M, Dirlik M, Tamer L, Ogetman Z, Polat Y, Kanik A, Aydin S. Liver tissue inducible nitric oxide synthase (iNOS) expression and lipid peroxidation in experiment alhepatic ischemia reperfusion injury stimulated with lipopolysaccharide:the role of am inoguanidine. J Surg Res 2008;148(2):214-223
    21 Jang YY, Suh ES, Kim WT. Retinal protective effects of minocycline via anti-apoptosis on oxygen-induced retinopathy i??????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????
    Cited by
    Comments
    Comments
    分享到微博
    Submit
Get Citation

An-Jie Du, Bing Ren, Xiao-Wei Gao,/et al.Effects of aminoguanidine on retinal apoptosis in mice with oxygen-induced retinopathy. Int J Ophthalmol, 2013,6(4):436-441

Copy
Share
Article Metrics
  • Abstract:1919
  • PDF: 1105
  • HTML: 0
  • Cited by: 0
Publication History
  • Received:November 21,2012
  • Revised:June 26,2013
  • Adopted:June 26,2013
  • Online: August 22,2013