Abstract | PURPOSE: METHODS:
Cloricromene (10 mg/kg intraperitoneally) was administered daily in diabetic rats, and 60 days later eyes were enucleated for localization of nitrotyrosine, ICAM-1, VEGF, ZO-1, occludin, claudin-5, and VE-cadherin by immunohistochemical analysis. The effect of treatment was also evaluated by TNFalpha, ICAM-1, VEGF, and eNOS protein levels measurement in the retina with the respective ELISA kits. Blood-retinal barrier (BRB) integrity was also evaluated by Evans blue. RESULTS: Increased amounts of cytokines, adhesion molecule, and nitric oxide synthase were observed in retina. Cloricromene treatment significantly lowered retinal TNFalpha, ICAM-1, VEGF, and eNOS. Furthermore, immunohistochemical analysis for VEGF, ICAM-1, nitrotyrosine (a marker of peroxynitrite), and tight junctions revealed positive staining in the retina from STZ-treated rats. The degree of staining for VEGF, ICAM-1, nitrotyrosine, and tight junctions was markedly reduced in tissue sections obtained from diabetic rats treated with cloricromene. Treatment with cloricromene suppressed diabetes-related BRB breakdown by 45%. CONCLUSIONS:
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Authors | Claudio Bucolo, Keith W Ward, Emanuela Mazzon, Salvatore Cuzzocrea, Filippo Drago |
Journal | Investigative ophthalmology & visual science
(Invest Ophthalmol Vis Sci)
Vol. 50
Issue 8
Pg. 3846-52
(Aug 2009)
ISSN: 1552-5783 [Electronic] United States |
PMID | 19279317
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antigens, CD
- Cadherins
- Claudin-5
- Cldn5 protein, rat
- Membrane Proteins
- Occludin
- Ocln protein, rat
- Phosphoproteins
- Platelet Aggregation Inhibitors
- Tjp1 protein, rat
- Tumor Necrosis Factor-alpha
- Vascular Endothelial Growth Factor A
- Zonula Occludens-1 Protein
- cadherin 5
- vascular endothelial growth factor A, rat
- Intercellular Adhesion Molecule-1
- 3-nitrotyrosine
- Tyrosine
- cloricromen
- Nitric Oxide Synthase Type III
- Nos3 protein, rat
- Chromonar
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Topics |
- Animals
- Antigens, CD
(metabolism)
- Blood-Retinal Barrier
(drug effects)
- Blotting, Western
- Cadherins
(metabolism)
- Chromonar
(analogs & derivatives, therapeutic use)
- Claudin-5
- Diabetes Mellitus, Experimental
(drug therapy, metabolism, pathology)
- Diabetic Retinopathy
(drug therapy, metabolism, pathology)
- Enzyme-Linked Immunosorbent Assay
- Immunohistochemistry
- Injections, Intraperitoneal
- Intercellular Adhesion Molecule-1
(metabolism)
- Male
- Membrane Proteins
(metabolism)
- Nitric Oxide Synthase Type III
(metabolism)
- Occludin
- Phosphoproteins
(metabolism)
- Platelet Aggregation Inhibitors
(therapeutic use)
- Rats
- Rats, Sprague-Dawley
- Tumor Necrosis Factor-alpha
(metabolism)
- Tyrosine
(analogs & derivatives, metabolism)
- Vascular Endothelial Growth Factor A
(metabolism)
- Zonula Occludens-1 Protein
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