Postconditioning with inhaled carbon monoxide counteracts apoptosis and neuroinflammation in the ischemic rat retina

Abstract: PurposeIschemia and reperfusion injury (I/R) of neuronal structures and organs is associated with increased morbidity and mortality due to neuronal cell death. We hypothesized that inhalation of carbon monoxide (CO) after I/R injury (‘postconditioning’) would protect retinal ganglion cells (RGC).MethodsRetinal I/R injury was performed in Sprague-Dawley rats (n=8) by increasing ocular pressure (120 mmHg, 1 h). Rats inhaled room air or CO (250 ppm) for 1 h immediately following ischemia or with 1.5 and 3 h latency. Retinal tissue was harvested to analyze Bcl-2, Bax, Caspase-3, HO-1 expression and phosphorylation of the nuclear transcription factor (NF)-κB, p38 and ERK-1/2 MAPK. NF-κB activation was determined and inhibition of ERK-1/2 was performed using PD98059 (2 mg/kg). Densities of fluorogold prelabeled RGC were analyzed 7 days after injury. Microglia, macrophage and Müller cell activation and proliferation were evaluated by Iba-1, GFAP and Ki-67 staining.ResultsInhalation of CO after I/R inhibited Bax and Caspase-3 expression (Bax: 1.9±0.3 vs. 1.4±0.2, p=0.028; caspase-3: 2.0±0.2 vs. 1.5±0.1, p=0.007; mean±S.D., fold induction at 12 h), while expression of Bcl-2 was induced (1.2±0.2 vs. 1.6±0.2, p=0.001; mean±S.D., fold induction at 12 h). CO postconditioning suppressed retinal p38 phosphorylation (p=0.023 at 24 h) and induced the phosphorylation of ERK-1/2 (p<0.001 at 24 h). CO postconditioning inhibited the expression of HO-1. The activation of NF-κB, microglia and Müller cells was potently inhibited by CO as well as immigration of proliferative microglia and macrophages into the retina. CO protected I/R-injured RGC with a therapeutic window at least up to 3 h (n=8; RGC/mm2; mean±S.D.: 1255±327 I/R only vs. 1956±157 immediate CO treatment, vs. 1830±109 1.5 h time lag and vs. 1626±122 3 h time lag; p<0.001). Inhibition of ERK-1/2 did not counteract the CO effects (RGC/mm2: 1956±157 vs. 1931±124, mean±S.D., p=0.799).ConclusionInhaled CO, administered after retinal ischemic injury, protects RGC through its strong anti-apoptotic and anti-inflammatory effects

Object Details

• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch
• Notes: PLoS ONE. 7, 9 (2012), e46479, DOI 10.1371/journal.pone.0046479, issn: 1932-6203 ; IN COPYRIGHT http://rightsstatements.org/page/InC/1.0 rs

Classification and Topics

• Keyword: Apoptosis ; Kohlenmonoxid ; Inhalation ; Entzündung ; Augenheilkunde ; Augenkrankheit

Contributors, Places and Time

• Event: Veröffentlichung
• (where): Freiburg
• (who): Universität
• (when): 2012
• Creator: Schallner, Nils ; Fuchs, Matthias ; Schwer, Christian Ingo ; Loop, Torsten ; Bürkle, Hartmut ; Lagrèze, Wolf A. ; Oterendorp, Christian van ; Biermann, Julia ; Göbel, Ulrich
• Contributor: Klinik für Augenheilkunde ; Anaesthesiologische Universitäts-Klinik ; Medizinische Fakultät ; Albert-Ludwigs-Universität Freiburg

Further information

• DOI: 10.1371/journal.pone.0046479
• URN: urn:nbn:de:bsz:25-freidok-118932
• Rights: Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Last update: 25.03.2025, 1:52 PM CET