The DOI matches its Crossref record; 48 of the 48 references it cites were found in a registry or an index.
Müller Cell-Derived VEGF Is Essential for Diabetes-Induced Retinal Inflammation and Vascular Leakage
Open accessAbstract
OBJECTIVE: Vascular endothelial growth factor (VEGF-A or VEGF) is a major pathogenic factor and therapeutic target for diabetic retinopathy (DR). Since VEGF has been proposed as a survival factor for retinal neurons, defining the cellular origin of pathogenic VEGF is necessary for the effectiveness and safety of long-term anti-VEGF therapies for DR. To determine the significance of Müller cell-derived VEGF in DR, we disrupted VEGF in Müller cells with an inducible Cre/lox system and examined diabetes-induced retinal inflammation and vascular leakage in these conditional VEGF knockout (KO) mice. RESEARCH DESIGN AND METHODS: Leukostasis was determined by counting the number of fluorescently labeled leukocytes inside retinal vasculature. Expression of biomarkers for retinal inflammation was assessed by immunoblotting of TNF-α, ICAM-1, and NF-κB. Vascular leakage was measured by immunoblotting of retinal albumin and fluorescent microscopic analysis of extravascular albumin. Diabetes-induced vascular alterations were examined by immunoblotting and immunohistochemistry for tight junctions, and by trypsin digestion assays for acellular capillaries. Retinal integrity was analyzed with morphologic and morphometric analyses. RESULTS: Diabetic conditional VEGF KO mice exhibited significantly reduced leukostasis, expression of inflammatory biomarkers, depletion of tight junction proteins, numbers of acellular capillaries, and vascular leakage compared to diabetic control mice. CONCLUSIONS: Müller cell-derived VEGF plays an essential and causative role in retinal inflammation, vascular lesions, and vascular leakage in DR. Therefore, Müller cells are a primary cellular target for proinflammatory signals that mediates retinal inflammation and vascular leakage in DR.
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Antonetti, D. A., Klein, R., & Gardner, T. W. (2012) · New England Journal of Medicine · doi:10.1056/nejmra1005073 · Cited by 1,659
Diabetic retinopathy: current understanding, mechanisms, and treatment strategies
Duh, E. J., Sun, J. K., & Stitt, A. W. (2017) · JCI Insight · doi:10.1172/jci.insight.93751 · Cited by 1,057
Xu, G.-T., Zhang, J.-F., & Tang, L. (2023) · Neural Regeneration Research · doi:10.4103/1673-5374.355743 · Cited by 280
Good News–Bad News: The Yin and Yang of Immune Privilege in the Eye
Forrester, J. V., & Xu, H. (2012) · Frontiers in Immunology · doi:10.3389/fimmu.2012.00338 · Cited by 153
Innate Immune Response in Retinal Homeostasis and Inflammatory Disorders
Murakami, Y., Ishikawa, K., Nakao, S., & Sonoda, K.-H. (2020) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2019.100778 · Cited by 125
Metadata
- Authors
- Wang, J., Xu, X., Elliott, M. H., Zhu, M., & Le, Y.-Z.
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2010-06-08
- Volume
- 59
- Issue
- 9
- Pages
- 2297-2305
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2124736173
- Cited by
- 396
- References
- 48
- FWCI
- 19.45
- Type
- journal article
- Language
- en
- Open access
- hybrid
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