Inhibitory effects of the platelet-activating factor receptor antagonists, CV-3988 and Ginkgolide B, on alkali burn-induced corneal neovascularization.

Abstract

PURPOSE:

Platelet-activating factor (PAF) has been found in various ocular tissues; the activity of PAF depends on the binding to its specific receptor, PAF-receptor. We investigated the therapeutic effects of PAF-receptor antagonists (CV-3988 and Ginkgolide B) on alkali burn-induced corneal neovascularization (CNV).

METHODS:

CNV was induced by applying a 0.2 N sodium hydroxide (3 µl, NaOH) solution directly on mice corneas. CV-3988 (1 mM/10 µl) and Ginkgolide B (1 mM/10 µl) were administered topically on the corneas three times daily for three consecutive days. CNV was evaluated under a slit-lamp microscope. Corneas were processed for histological, immunohistochemical and reverse transcription polymerase chain reaction analysis. Human umbilical vein endothelial cells were used for the migration and tube formation assay.

RESULTS:

Application of CV-3988 and Ginkgolide B inhibited CNV caused by alkali burn. CV-3988 and Ginkgolide B attenuated the expression of PAF-receptor mRNA. Alkali injury induced a massively increased intraocular mRNA expression of an angiogenic factor in cornea tissues, whereas these increments were attenuated by the application of CV-3988 and Ginkgolide B.

CONCLUSIONS:

CV-3988 and Ginkgolide B reversed opacity and neovascularization in alkali burn-induced corneas. Our findings suggest that CV-3988 and Ginkgolide B may be therapeutically useful in the treatment of CNV and inflammation.

• Authors: Chang-Min Lee, Won-Kyo Jung, Giyoun Na, Dae-Sung Lee, Sae-Gwang Park, Su-Kil Seo, Jae-Wook Yang, Sung Su Yea, Young-Min Lee, Won Sun Park, Il-Whan Choi
• Journal: Cutaneous and ocular toxicology (Cutan Ocul Toxicol) Vol. 34 Issue 1 Pg. 53-60 (Mar 2015) ISSN: 1556-9535 [Electronic] England
• PMID: 24754407 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Alkalies
• Ginkgolides
• Lactones
• Phospholipid Ethers
• Platelet Aggregation Inhibitors
• Platelet Membrane Glycoproteins
• RNA, Messenger
• Receptors, G-Protein-Coupled
• platelet activating factor receptor
• CV 3988
• ginkgolide B

Topics

• Alkalies (adverse effects)
• Animals
• Cell Movement (drug effects)
• Cells, Cultured
• Corneal Injuries (chemically induced)
• Corneal Neovascularization (drug therapy, pathology)
• Corneal Opacity (drug therapy)
• Eye Burns (chemically induced, drug therapy, pathology)
• Female
• Ginkgolides (pharmacology, therapeutic use)
• Human Umbilical Vein Endothelial Cells (drug effects, physiology)
• Humans
• Lactones (pharmacology, therapeutic use)
• Mice
• Neovascularization, Physiologic (drug effects)
• Neutrophils (drug effects)
• Phospholipid Ethers (pharmacology, therapeutic use)
• Platelet Aggregation Inhibitors (pharmacology, therapeutic use)
• Platelet Membrane Glycoproteins (antagonists & inhibitors, genetics)
• RNA, Messenger (metabolism)
• Receptors, G-Protein-Coupled (antagonists & inhibitors, genetics)