Larger therapeutic window for steroid versus VEGF-A inhibitor in inflammatory angiogenesis: Surprisingly similar impact on leukocyte infiltration

Shintaro Nakao, Souska Zandi, Nuria Lara-Castillo, Mahdi Taher, Tatsuro Ishibashi, Ali Hafezi-Moghadam

研究成果: Contribution to journalArticle査読

27 被引用数 (Scopus)

抄録

Purpose. The current treatments against inflammatory angiogenesis are steroids and anti-VEGF-A, such as dexamethasone and bevacizumab, respectively. However, the therapeutic windows for dexamethasone and bevacizumab against inflammatory angiogenesis are unknown. Methods. To investigate the therapeutic windows for dexamethasone and bevacizumab, we used the corneal pocket assay. IL-1β pellets were implanted in corneas of BALB/c mice that were then treated with dexamethasone or bevacizumab at different time points. Angiogenesis (area, number of vessels, and sprouting) was quantitated at various time points after implantation. Nuclear Factor-κB (NF-κB) signaling and leukocyte accumulation in inflammatory angiogenesis were examined by Western blotting, by immunohistochemistry, and in the authors' novel leukocyte transmigration assay. Results. Dexamethasone inhibited IL-1β-induced angiogenesis when treatment started 4 days after IL-1β implantation, while bevacizumab only inhibited angiogenesis by day 2 after implantation. Both bevacizumab and dexamethasone inhibited angiogenic sprouting. Interestingly, bevacizumab did not affect NF-κB activation, which is one of the main signaling targets for steroid action. The authors' new imaging approach revealed that bevacizumab and steroid treatment blocked leukocyte infiltration into implanted corneas. Conclusions. VEGF-A inhibition affected angiogenic sprouting, while it was not effective against matured vessels. Both dexamethasone and bevacizumab inhibited leukocyte transmigration from angiogenic vessels; however, dexamethasone had a larger therapeutic window. These insights improve the treatment strategy in angiogenic disorders.

本文言語英語
ページ(範囲)3296-3302
ページ数7
ジャーナルInvestigative Ophthalmology and Visual Science
53
7
DOI
出版ステータス出版済み - 6 2012

All Science Journal Classification (ASJC) codes

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

フィンガープリント 「Larger therapeutic window for steroid versus VEGF-A inhibitor in inflammatory angiogenesis: Surprisingly similar impact on leukocyte infiltration」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル