title: Retinal protection from acute glaucoma-induced ischemia-reperfusion injury through pharmacologic induction of heme oxygenase-1.
abstract: OBJECTIVE
  To investigate the protective effects of cobalt protoporphyrin (CoPP), a potent heme oxygenase (HO)-1 inducer, in a rat model of ischemia-reperfusion injury and to document the possible antiapoptotic and anti-inflammatory mechanisms underlying the protection.
  
  
  METHODS
  Rats pretreated with intraperitoneal injection of CoPP (5 mg/kg) were subjected to retinal ischemia by increases in intraocular pressure to 130 mm Hg for 60 minutes. The protective effects of CoPP were evaluated by determining the morphology of the retina, counting the survival of retinal ganglion cells (RGCs), and measuring apoptosis in retinal layers. In addition, expressions of HO-1, caspase-3, p53, Bcl-xL, monocyte chemoattractant protein (MCP)-1, and inducible nitric oxide synthase (iNOS) were documented by Western blot analysis. Detection of HO-1, NF-kappaB, and CD68 protein in the retina was performed by immunohistochemistry or immunofluorescence.
  
  
  RESULTS
  Pharmacologic induction of HO-1 by CoPP led to HO-1 expression in the full retinal layer. HO-1 overexpression alleviated apoptosis in the retina, preserved RGCs, and attenuated the reduction of inner retinal thickness after ischemia-reperfusion injury. Concurrently, overexpression of HO-1 was associated with inhibition of caspase-3, p53, NF-kappaB, and iNOS and with increased expression of Bcl-xL. Meanwhile, the anti-inflammatory effect of HO-1 was related to reduction in the recruitment of macrophage infiltration in the retina through the suppression of MCP-1. These beneficial effects of HO-1 induced by CoPP were diminished by the HO-1 inhibitor ZnPP.
  
  
  CONCLUSIONS
  Overexpression of HO-1 by pharmacologic induction protected the retina from subsequent cellular damage caused by ischemia-reperfusion injury through antiapoptotic and anti-inflammatory effects.
authors.affiliation: Department of Ophthalmology, Chang Gung Memorial Hospital, Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Ming-Hui
authors.initials: MH
authors.lastname: Sun
authors.forename: Jong-Hwei Su
authors.initials: JH
authors.lastname: Pang
authors.forename: Show-Li
authors.initials: SL
authors.lastname: Chen
authors.forename: Wen-Hua
authors.initials: WH
authors.lastname: Han
authors.forename: Tsung-Chuan
authors.initials: TC
authors.lastname: Ho
authors.forename: Kuan-Jen
authors.initials: KJ
authors.lastname: Chen
authors.forename: Ling-Yuh
authors.initials: LY
authors.lastname: Kao
authors.forename: Ken-Kuo
authors.initials: KK
authors.lastname: Lin
authors.forename: Yeou-Ping
authors.initials: YP
authors.lastname: Tsao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D018932:Chemokine CCL2 / Q000378:metabolism; D002829:Choroid / Q000098:blood supply / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D005901:Glaucoma / Q000150:complications* / Q000188:drug therapy* / Q000473:pathology; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D007429:Intraocular Pressure; D008264:Macrophages / Q000187:drug effects / Q000473:pathology; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D011524:Protoporphyrins / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology; D012160:Retina / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D051996:Transcription Factor RelA / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: C494813:Bcl2l1 protein, rat; C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D011524:Protoporphyrins; D051996:Transcription Factor RelA; D016159:Tumor Suppressor Protein p53; D051020:bcl-X Protein; C007095:cobaltiprotoporphyrin; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D051547:Heme Oxygenase-1; C505410:Casp3 protein, rat; D053148:Caspase 3