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Article: Expression of hypoxia-inducible factor-1α and -2α in human choroidal neovascular membranes

TitleExpression of hypoxia-inducible factor-1α and -2α in human choroidal neovascular membranes
Authors
KeywordsChoroidalneo vascular membranes
Cytokine expression
Hypoxia
RPE
Issue Date2009
PublisherSpringer Verlag. The Journal's web site is located at http://link.springer.de/link/service/journals/00417/index.htm
Citation
Graefe's Archive For Clinical And Experimental Ophthalmology, 2009, v. 247 n. 10, p. 1361-1367 How to Cite?
AbstractPurpose: Up-regulation of pro-angiogenic cytokine expression occurring secondary to hypoxia in physiologic and pathophysiologic conditions is mediated by the family of transcription regulators know as hypoxia inducible factors (HIF). The present study was undertaken to investigate the expression of HIF occurring in human choroidal neovascularization (CNV) and the posterior segment of young and old eyes. Methods: Surgically excised CNV from patients with either age-related macular degeneration (AMD; n = 9), punctuate inner choroidopathy (PIC; n = 3) and young normal eyes were immunohistochemically probed with monoclonal antibodies against HIF-1α and -2α and compared to that for cell markers specific for vascular endothelial cells (CD34), macrophages (CD68), retinal pigment epithelial cells (RPE; panel cytokeratins/CK18) and VEGF. Following secondary antibody amplification, reactions were visualized with fast red chromogen. Results: Cellular immunoreactivity of membranes for HIF-2α was strong in eight out of nine AMD specimens but it was only weakly positive for HIF-1α in five specimens. In contrast, two out of three PIC specimens were weakly positive for HIF-1α but demonstrated no staining for HIF-2α. Immunohistochemical analysis revealed areas within the CNV membranes that were predominantly immunopositive for CD68 and cytokeratin indicating the presence of RPE and/or macrophages and that these cells strongly co-localized with the presence of HIF and VEGF. No immunochemical co-localization was observed with HIF and the endothelial cell marker CD34 in any membranes studied. Normal globes also demonstrated HIF-2 positivity to be predominantly localized to the central RPE rather than peripheral RPE irrespective of age of donor. Conclusions: The localization of HIF expression supports the concept that hypoxia is a major stimulus for the development of submacular wound healing and within this context CNV is but one component of this process. © Springer-Verlag 2009.
Persistent Identifierhttp://hdl.handle.net/10722/146306
ISSN
2015 Impact Factor: 1.991
2015 SCImago Journal Rankings: 1.217
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorSheridan, CMen_HK
dc.contributor.authorPate, Sen_HK
dc.contributor.authorHiscott, Pen_HK
dc.contributor.authorWong, Den_HK
dc.contributor.authorPattwell, DMen_HK
dc.contributor.authorKent, Den_HK
dc.date.accessioned2012-04-10T01:50:06Z-
dc.date.available2012-04-10T01:50:06Z-
dc.date.issued2009en_HK
dc.identifier.citationGraefe's Archive For Clinical And Experimental Ophthalmology, 2009, v. 247 n. 10, p. 1361-1367en_HK
dc.identifier.issn0721-832Xen_HK
dc.identifier.urihttp://hdl.handle.net/10722/146306-
dc.description.abstractPurpose: Up-regulation of pro-angiogenic cytokine expression occurring secondary to hypoxia in physiologic and pathophysiologic conditions is mediated by the family of transcription regulators know as hypoxia inducible factors (HIF). The present study was undertaken to investigate the expression of HIF occurring in human choroidal neovascularization (CNV) and the posterior segment of young and old eyes. Methods: Surgically excised CNV from patients with either age-related macular degeneration (AMD; n = 9), punctuate inner choroidopathy (PIC; n = 3) and young normal eyes were immunohistochemically probed with monoclonal antibodies against HIF-1α and -2α and compared to that for cell markers specific for vascular endothelial cells (CD34), macrophages (CD68), retinal pigment epithelial cells (RPE; panel cytokeratins/CK18) and VEGF. Following secondary antibody amplification, reactions were visualized with fast red chromogen. Results: Cellular immunoreactivity of membranes for HIF-2α was strong in eight out of nine AMD specimens but it was only weakly positive for HIF-1α in five specimens. In contrast, two out of three PIC specimens were weakly positive for HIF-1α but demonstrated no staining for HIF-2α. Immunohistochemical analysis revealed areas within the CNV membranes that were predominantly immunopositive for CD68 and cytokeratin indicating the presence of RPE and/or macrophages and that these cells strongly co-localized with the presence of HIF and VEGF. No immunochemical co-localization was observed with HIF and the endothelial cell marker CD34 in any membranes studied. Normal globes also demonstrated HIF-2 positivity to be predominantly localized to the central RPE rather than peripheral RPE irrespective of age of donor. Conclusions: The localization of HIF expression supports the concept that hypoxia is a major stimulus for the development of submacular wound healing and within this context CNV is but one component of this process. © Springer-Verlag 2009.en_HK
dc.languageengen_US
dc.publisherSpringer Verlag. The Journal's web site is located at http://link.springer.de/link/service/journals/00417/index.htmen_HK
dc.relation.ispartofGraefe's Archive for Clinical and Experimental Ophthalmologyen_HK
dc.subjectChoroidalneo vascular membranesen_HK
dc.subjectCytokine expressionen_HK
dc.subjectHypoxiaen_HK
dc.subjectRPEen_HK
dc.subject.meshAdulten_US
dc.subject.meshAgeden_US
dc.subject.meshAged, 80 And Overen_US
dc.subject.meshAntigens, Cd - Metabolismen_US
dc.subject.meshAntigens, Cd34 - Metabolismen_US
dc.subject.meshAntigens, Differentiation, Myelomonocytic - Metabolismen_US
dc.subject.meshAryl Hydrocarbon Receptor Nuclear Translocator - Metabolismen_US
dc.subject.meshChoroid - Metabolismen_US
dc.subject.meshChoroidal Neovascularization - Etiology - Metabolism - Pathologyen_US
dc.subject.meshEye Banksen_US
dc.subject.meshFemaleen_US
dc.subject.meshHumansen_US
dc.subject.meshHypoxia-Inducible Factor 1, Alpha Subunit - Metabolismen_US
dc.subject.meshImmunohistochemistry - Methodsen_US
dc.subject.meshKeratins - Metabolismen_US
dc.subject.meshMacular Degeneration - Complicationsen_US
dc.subject.meshMaleen_US
dc.subject.meshMiddle Ageden_US
dc.subject.meshRetinal Pigment Epithelium - Metabolism - Pathologyen_US
dc.subject.meshStaining And Labelingen_US
dc.subject.meshTissue Distributionen_US
dc.titleExpression of hypoxia-inducible factor-1α and -2α in human choroidal neovascular membranesen_HK
dc.typeArticleen_HK
dc.identifier.emailWong, D: shdwong@hku.hken_HK
dc.identifier.authorityWong, D=rp00516en_HK
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1007/s00417-009-1133-3en_HK
dc.identifier.pmid19590888-
dc.identifier.scopuseid_2-s2.0-69549118436en_HK
dc.identifier.hkuros165342-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-69549118436&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume247en_HK
dc.identifier.issue10en_HK
dc.identifier.spage1361en_HK
dc.identifier.epage1367en_HK
dc.identifier.isiWOS:000269320000008-
dc.publisher.placeGermanyen_HK
dc.identifier.scopusauthoridSheridan, CM=7004974390en_HK
dc.identifier.scopusauthoridPate, S=40262227100en_HK
dc.identifier.scopusauthoridHiscott, P=7006368693en_HK
dc.identifier.scopusauthoridWong, D=7401536078en_HK
dc.identifier.scopusauthoridPattwell, DM=6505863976en_HK
dc.identifier.scopusauthoridKent, D=35512364500en_HK
dc.identifier.citeulike5125195-

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