title: Alteration of retinal intrinsic survival signal and effect of alpha2-adrenergic receptor agonist in the retina of the chronic ocular hypertension rat.
abstract: The purpose of this study is to examine the retinal expression of intrinsic cell survival molecules and to elucidate the effect of an alpha2-adrenergic receptor agonist in the chronic ocular hypertensive rat model. Chronic ocular hypertension was induced in both eyes of each rat by episcleral vein cauterization. Two five-microliter drops of the selective alpha2-adrenoceptor agonist brimonidine 0.2% (Alphagan; Allergan Inc., Irvine, CA, USA) were topically administered twice daily for up to eight weeks in one eye. The fellow eye received balanced salt solution as a control. Protein and mRNA expression were evaluated at 1, 4, and 8 weeks after injury. Retinal expression of BDNF, Akt, and GFAP was assessed using immunohistochemistry. Retinal levels of mRNA for BDNF, bcl-2, and bcl-xL were determined using semi-quantitative RT-PCR. Retinal ganglion cell (RGC) density was evaluated after retrograde labeling with 4-Di-10-ASP (DiA). A significant decrease in RGC density was observed in ocular hypertensive eyes. Cauterized eyes showed an increase in GFAP expression from one week after injury, and the expression of bcl-2, bcl-xL, and BDNF mRNA was also increased. Treatment of ocular hypertensive eyes with brimonidine resulted in a reduction in RGC loss, a decrease in the level of GFAP immunoreactivity, and an increment in BDNF mRNA and p-Akt expression. Brimonidine appears to protect RGCs from neurodegeneration through mechanisms involving alpha2-adrenergic receptor mediated survival signal activation and up-regulation of endogenous neurotrophic factor expression in the chronic ocular hypertensive rat retina.
authors.affiliation: Department of Ophthalmology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Hwa Sun
authors.initials: HS
authors.lastname: Kim
authors.forename: Yong Ik
authors.initials: YI
authors.lastname: Chang
authors.forename: Jie Hyun
authors.initials: JH
authors.lastname: Kim
authors.forename: Chan Kee
authors.initials: CK
authors.lastname: Park
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000627:therapeutic use*; D000704:Analysis of Variance; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D000068438:Brimonidine Tartrate; D002452:Cell Count / Q000379:methods; D002908:Chronic Disease; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D008297:Male; D009798:Ocular Hypertension / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D051058:Oncogene Protein v-akt / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D011726:Pyridinium Compounds; D011810:Quinoxalines / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012165:Retinal Ganglion Cells / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013997:Time Factors
chemical_list: D000316:Adrenergic alpha-Agonists; D019208:Brain-Derived Neurotrophic Factor; D005904:Glial Fibrillary Acidic Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D011726:Pyridinium Compounds; D011810:Quinoxalines; D012333:RNA, Messenger; C076868:4-(4-dihexadecylaminostyryl)-N-methylpyridium; D000068438:Brimonidine Tartrate; D051058:Oncogene Protein v-akt