Please use this identifier to cite or link to this item: http://hdl.handle.net/1959.14/138007
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- Title
- Endostatin modulates VEGF-mediated barrier dysfunction in the retinal microvascular endothelium
- Related
- Experimental eye research, Vol. 81, Issue 1, (2005), p.22-31
- DOI
- 10.1016/j.exer.2005.01.005
- Publisher
- Elsevier
- Date
- 2005
- Author/Creator
- Brankin, Brenda
- Author/Creator
- Campbell, Matthew P
- Author/Creator
- Canning, P
- Author/Creator
- Gardiner, T.A
- Author/Creator
- Stitt, Alan W
- Description
- Recent evidence indicates that the anti-angiogenic peptide endostatin may modulate some of the vasomodulatory effects of vascular endothelial growth factor (VEGF) in the retina, including reduction of blood retinal barrier function although it remains uncertain how endostatin promotes endothelial barrier properties. The current study has sought to examine how physiological levels of endostatin alters VEGF-induced inner BRB function using an in vitro model system and evaluation of occludin and ZO-1 regulatory responses. In addition, the ability of exogenous endostatin to regulate VEGF-mediated retinal vascular permeability in vivo was investigated. Retinal microvascular endothelial cells (RMEC's) were exposed to various concentrations of endostatin. In parallel studies, RMEC monolayers were treated with vascular endothelial growth factor (VEGF₁₆₅). Vasopermeability of RMEC monolayers and occludin expression were determined. Blood retinal barrier integrity was quantified in mouse retina using Evans Blue assay following intravitreal delivery of VEGF₁₆₅, endostatin or a VEGF/endostatin combination. Endostatin increased the levels of expression of occludin whilst causing no significant change in FITC-dextran flux across the RMEC monolayer. Endostatin reversed the effects of VEGF₁₆₅-enhanced permeability between microvascular endothelial cells and induced phosphorylation of occludin. Evans Blue leakage from retinas treated with VEGF was 2.0 fold higher than that of contra-lateral untreated eyes (P<0.05) while leakage of eyes from endostatin treated animals was unchanged. When eyes were injected with a combination of VEGF₁₆₅ and endostatin there was a significant reduction in retinal vasopermeability when compared to VEGF-injected eyes (P<0.05). We conclude that endostatin can promote integrity of the retinal endothelial barrier, possibly by preventing VEGF-mediated alteration of tight junction integrity. This suggests that endostatin may be of clinical benefit in ocular disorders where significant retinal vasopermeability changes are present.
- Description
- 10 page(s)
- Subject Keyword
- tight junctions
- Subject Keyword
- occludin
- Subject Keyword
- blood–retinal barrier
- Subject Keyword
- endostatin
- Subject Keyword
- VEGF
- Subject Keyword
- Evan's blue
- Resource Type
- journal article
- Organisation
- Macquarie University. Dept. of Chemistry and Biomolecular Sciences
- Identifier
- http://hdl.handle.net/1959.14/138007
- Identifier
- ISSN:0014-4835
- Identifier
- mq_res-ext-201109230829-35
- Language
- eng
- Reviewed
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