Abstract | OBJECTIVE: METHODS: Bone marrow cells were collected from the femurs and tibias of wild type and NOX2 deficient (NOX2(-/-)) donor mice and injected intravenously into lethally irradiated NOX2(-/-) and wild type recipients. Following recovery from radiation, mice were rendered diabetic by streptozotocin injections. The following groups of bone marrow chimeras were studied: non-diabetic WT → WT, diabetic WT → WT, diabetic WT → NOX2(-/-), diabetic NOX2(-/-) → WT. After 4 weeks of diabetes, early signs of retinopathy were examined by measuring ROS, expression of VEGF and ICAM-1, leukocyte attachment to the vessel wall and vascular permeability. RESULTS: The retinas of the diabetic WT → WT chimeras showed significant increases in ROS as compared with the non-diabetic chimeras. These diabetes-induced alterations were correlated with increases in expression of VEGF and ICAM-1, leukocyte adhesion and vascular permeability. Each of these diabetes-induced alterations were significantly attenuated in the diabetic WT → NOX2(-/-) and NOX2(-/-) → WT chimera groups (p<0.05). CONCLUSION: NOX2-generated ROS produced by both bone marrow-derived cells and resident retinal cells contribute importantly to retinal vascular injury in the diabetic retina. Targeting NOX2 in bone marrow and/or retinal cells may represent a novel therapeutic strategy for the treatment/prevention of vascular injury in the diabetic retina.
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Authors | Modesto Rojas, Wenbo Zhang, Zhimin Xu, Tahira Lemtalsi, Phillip Chandler, Haroldo A Toque, Robert W Caldwell, Ruth B Caldwell |
Journal | PloS one
(PLoS One)
Vol. 8
Issue 12
Pg. e84357
( 2013)
ISSN: 1932-6203 [Electronic] United States |
PMID | 24358357
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
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Chemical References |
- Membrane Glycoproteins
- Vascular Endothelial Growth Factor A
- Intercellular Adhesion Molecule-1
- Peroxynitrous Acid
- Tyrosine
- Cybb protein, mouse
- NADPH Oxidase 2
- NADPH Oxidases
- Leukocyte Common Antigens
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Topics |
- Animals
- Blood-Retinal Barrier
(metabolism, pathology)
- Bone Marrow
(metabolism)
- Cell Adhesion
- Chimera
- Diabetes Mellitus, Experimental
- Diabetic Retinopathy
(genetics, metabolism, pathology)
- Gene Expression
- Genotype
- Intercellular Adhesion Molecule-1
(metabolism)
- Leukocyte Common Antigens
(metabolism)
- Leukocytes
(metabolism)
- Male
- Membrane Glycoproteins
(genetics, metabolism)
- Mice
- Mice, Knockout
- NADPH Oxidase 2
- NADPH Oxidases
(genetics, metabolism)
- Oxidative Stress
(genetics)
- Peroxynitrous Acid
(biosynthesis)
- Retina
(metabolism)
- Tyrosine
(metabolism)
- Vascular Endothelial Growth Factor A
(metabolism)
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