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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Increased expression and activity of 12-lipoxygenase in oxygen-induced ischemic retinopathy and proliferative diabetic retinopathy: Implications in retinal neovascularization
Diabetes, Volume 60, No. 2, Year 2011
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Description
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 epithelium-derived factor (PEDF). Liquid chromatography-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-HETE-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. © 2011 by the American Diabetes Association.
Authors & Co-Authors
Al-Shabrawey, Mohamed
United States, Augusta
Medical College of Georgia
Saudi Arabia, Riyadh
College of Medicine
Egypt, Mansoura
Faculty of Medicine
Mussell, Rene
United States, Augusta
Medical College of Georgia
Kahook, Khalid
United States, Augusta
Medical College of Georgia
Tawfik, Amany M.
United States, Augusta
Medical College of Georgia
Eladl, Mohamed Ahmed
Egypt, Mansoura
Faculty of Medicine
Sarthy, Vijay P.
United States, Evanston
Northwestern University
Nussbaum, Julian J.
United States, Augusta
Medical College of Georgia
Elmarakby, Ahmed
United States, Augusta
Medical College of Georgia
Park, Sunyoung
United States, Madison
University of Wisconsin School of Medicine and Public Health
Gurel, Zafer
United States, Madison
University of Wisconsin School of Medicine and Public Health
Sheibani, Nader
United States, Madison
University of Wisconsin School of Medicine and Public Health
Maddipati, Krishnarao
United States, Detroit
Wayne State University
Statistics
Citations: 49
Authors: 12
Affiliations: 6
Identifiers
Doi:
10.2337/db10-0008
ISSN:
00121797
e-ISSN:
1939327X
Research Areas
Cancer
Health System And Policy
Noncommunicable Diseases