Increased Expression and Activity of 12-Lipoxygenase in Oxygen-Induced Ischemic Retinopathy and Proliferative Diabetic Retinopathy

Hdl Handle:
http://hdl.handle.net/10675.2/629
Title:
Increased Expression and Activity of 12-Lipoxygenase in Oxygen-Induced Ischemic Retinopathy and Proliferative Diabetic Retinopathy
Authors:
Al-Shabrawey, Mohamed ( 0000-0001-5362-7972 ) ; Mussell, Rene; Kahook, Khalid; Tawfik, Amany; Eladl, Mohamed; Sarthy, Vijay; Nussbaum, Julian; El-Marakby, Ahmed; Park, Sun Young; Gurel, Zafer; Sheibani, Nader; Maddipati, Krishna Rao
Abstract:
OBJECTIVE: Arachidonic acid is metabolized by 12-lipoxygenase (12-LOX) to 12-hydroxyeicosatetraenoic acid (12-HETE) and has an important role in the regulation of angiogenesis and endothelial cell proliferation and migration. The goal of this study was to investigate whether 12-LOX plays a role in retinal neovascularization (NV).; RESEARCH DESIGN AND METHODS: Experiments were performed using retinas from a murine model of oxygen-induced ischemic retinopathy (OIR) that was treated with and without the LOX pathway inhibitor, baicalein, or lacking 12-LOX. We also analyzed vitreous samples from patients with and without proliferative diabetic retinopathy (PDR). Western blotting and RT-PCR were used to assess the expression of 12-LOX, vascular endothelial growth factor (VEGF), and pigment epitheliumâ derived factor (PEDF). Liquid chromatographyâ mass spectrometry was used to assess the amounts of HETEs in the murine retina and human vitreous samples. The effects of 12-HETE on VEGF and PEDF expression were evaluated in Müller cells (rMCs), primary mouse retinal pigment epithelial cells, and astrocytes.; RESULTS: Retinal NV during OIR was associated with increased 12-LOX expression and 12-, 15-, and 5-HETE production. The amounts of HETEs also were significantly higher in the vitreous of diabetic patients with PDR. Retinal NV was markedly abrogated in mice treated with baicalein or mice lacking 12-LOX. This was associated with decreased VEGF expression and restoration of PEDF levels. PEDF expression was reduced in 12-HETEâ treated rMCs, astrocytes, and the retinal pigment epithelium. Only rMCs and astrocytes showed increased VEGF expression by 12-HETE.; CONCLUSIONS: 12-LOX and its product HETE are important regulators of retinal NV through modulation of VEGF and PEDF expression and could provide a new therapeutic target to prevent and treat ischemic retinopathy.
Citation:
Diabetes. 2011 Feb 21; 60(2):614-624
Issue Date:
21-Jan-2011
URI:
http://hdl.handle.net/10675.2/629
DOI:
10.2337/db10-0008
PubMed ID:
21228311
PubMed Central ID:
PMC3028363
Type:
Article
ISSN:
1939-327X
Appears in Collections:
Department of Oral Biology: Faculty Research and Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorAl-Shabrawey, Mohameden_US
dc.contributor.authorMussell, Reneen_US
dc.contributor.authorKahook, Khaliden_US
dc.contributor.authorTawfik, Amanyen_US
dc.contributor.authorEladl, Mohameden_US
dc.contributor.authorSarthy, Vijayen_US
dc.contributor.authorNussbaum, Julianen_US
dc.contributor.authorEl-Marakby, Ahmeden_US
dc.contributor.authorPark, Sun Youngen_US
dc.contributor.authorGurel, Zaferen_US
dc.contributor.authorSheibani, Naderen_US
dc.contributor.authorMaddipati, Krishna Raoen_US
dc.date.accessioned2012-10-26T16:26:55Z-
dc.date.available2012-10-26T16:26:55Z-
dc.date.issued2011-01-21en_US
dc.identifier.citationDiabetes. 2011 Feb 21; 60(2):614-624en_US
dc.identifier.issn1939-327Xen_US
dc.identifier.pmid21228311en_US
dc.identifier.doi10.2337/db10-0008en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/629-
dc.description.abstractOBJECTIVE: Arachidonic acid is metabolized by 12-lipoxygenase (12-LOX) to 12-hydroxyeicosatetraenoic acid (12-HETE) and has an important role in the regulation of angiogenesis and endothelial cell proliferation and migration. The goal of this study was to investigate whether 12-LOX plays a role in retinal neovascularization (NV).en_US
dc.description.abstractRESEARCH DESIGN AND METHODS: Experiments were performed using retinas from a murine model of oxygen-induced ischemic retinopathy (OIR) that was treated with and without the LOX pathway inhibitor, baicalein, or lacking 12-LOX. We also analyzed vitreous samples from patients with and without proliferative diabetic retinopathy (PDR). Western blotting and RT-PCR were used to assess the expression of 12-LOX, vascular endothelial growth factor (VEGF), and pigment epitheliumâ derived factor (PEDF). Liquid chromatographyâ mass spectrometry was used to assess the amounts of HETEs in the murine retina and human vitreous samples. The effects of 12-HETE on VEGF and PEDF expression were evaluated in Müller cells (rMCs), primary mouse retinal pigment epithelial cells, and astrocytes.en_US
dc.description.abstractRESULTS: Retinal NV during OIR was associated with increased 12-LOX expression and 12-, 15-, and 5-HETE production. The amounts of HETEs also were significantly higher in the vitreous of diabetic patients with PDR. Retinal NV was markedly abrogated in mice treated with baicalein or mice lacking 12-LOX. This was associated with decreased VEGF expression and restoration of PEDF levels. PEDF expression was reduced in 12-HETEâ treated rMCs, astrocytes, and the retinal pigment epithelium. Only rMCs and astrocytes showed increased VEGF expression by 12-HETE.en_US
dc.description.abstractCONCLUSIONS: 12-LOX and its product HETE are important regulators of retinal NV through modulation of VEGF and PEDF expression and could provide a new therapeutic target to prevent and treat ischemic retinopathy.en_US
dc.rights© 2011 by the American Diabetes Association.en_US
dc.subjectComplicationsen_US
dc.subject.meshAnalysis of Varianceen_US
dc.subject.meshAnimalsen_US
dc.subject.meshArachidonate 12-Lipoxygenaseen_US
dc.subject.meshBlotting, Westernen_US
dc.subject.meshDiabetic Retinopathyen_US
dc.subject.meshEnzyme Inhibitorsen_US
dc.subject.meshEnzyme-Linked Immunosorbent Assayen_US
dc.subject.meshEye Proteinsen_US
dc.subject.meshFlavanonesen_US
dc.subject.meshHumansen_US
dc.subject.meshHydroxyeicosatetraenoic Acidsen_US
dc.subject.meshImmunohistochemistryen_US
dc.subject.meshIschemiaen_US
dc.subject.meshMass Spectrometryen_US
dc.subject.meshMiceen_US
dc.subject.meshNerve Growth Factorsen_US
dc.subject.meshRetinal Neovascularizationen_US
dc.subject.meshRetinal Vesselsen_US
dc.subject.meshReverse Transcriptase Polymerase Chain Reactionen_US
dc.subject.meshSerpinsen_US
dc.subject.meshVascular Endothelial Growth Factor Aen_US
dc.subject.meshVitreous Bodyen_US
dc.titleIncreased Expression and Activity of 12-Lipoxygenase in Oxygen-Induced Ischemic Retinopathy and Proliferative Diabetic Retinopathyen_US
dc.typeArticleen_US
dc.identifier.pmcidPMC3028363en_US
dc.contributor.corporatenameDepartment of Oral Biology-
dc.contributor.corporatenameDepartment of Ophthalmology-
dc.contributor.corporatenameVision Discovery Institute-

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