Article ; Online: Intravitreal itraconazole inhibits laser-induced choroidal neovascularization in rats.
PloS one
2017 Volume 12, Issue 6, Page(s) e0180482
Abstract: ... that intravitreal itraconazole significantly inhibited the development of laser-induced CNV in rats. Itraconazole ... angiogenesis. We evaluated the anti-angiogenic effect of itraconazole in a rat model of laser-induced CNV ... with age-related macular degeneration (AMD). Recently, itraconazole has shown potent and dose-dependent inhibition of tumor-associated ...
Abstract | Choroidal neovascularization (CNV) is a major cause of severe visual loss in patients with age-related macular degeneration (AMD). Recently, itraconazole has shown potent and dose-dependent inhibition of tumor-associated angiogenesis. We evaluated the anti-angiogenic effect of itraconazole in a rat model of laser-induced CNV. After laser photocoagulation in each eye to cause CNV, right eyes were administered intravitreal injections of itraconazole; left eyes received balanced salt solution (BSS) as controls. On day 14 after laser induction, fluorescein angiography (FA) was used to assess abnormal vascular leakage. Flattened retinal pigment epithelium (RPE)-choroid tissue complex was stained with Alexa Fluor 594-conjugated isolectin B4 to measure the CNV area and volume. Vascular endothelial growth factor receptor 2 (VEGFR2) mRNA and protein expression was determined 1, 4, 7, and 14 days after intravitreal injection by quantitative RT-PCR or Western blot. VEGF levels were analyzed by enzyme-linked immunosorbent assay (ELISA). Intravitreal itraconazole significantly reduced leakage from CNV as assessed by FA and CNV area and volume on flat mounts compared with intravitreal BSS (p = 0.002 for CNV leakage, p<0.001 for CNV area and volume). Quantitative RT-PCR showed significantly lower expression of VEGFR2 mRNA in the RPE-choroid complexes of itraconazole-injected eyes than those of BSS-injected eyes on days 7 and 14 (p = 0.003 and p = 0.006). Western blots indicated that VEGFR2 was downregulated after itraconazole treatment. ELISA showed a significant difference in VEGF level between itraconazole-injected and BSS-injected eyes on days 7 and 14 (p = 0.04 and p = 0.001). Our study demonstrated that intravitreal itraconazole significantly inhibited the development of laser-induced CNV in rats. Itraconazole had anti-angiogenic activity along with the reduction of VEGFR2 and VEGF levels. Itraconazole may prove beneficial for treating CNV as an alternative or adjunct to other therapies. |
---|---|
MeSH term(s) | Animals ; Choroidal Neovascularization/etiology ; Choroidal Neovascularization/prevention & control ; Enzyme-Linked Immunosorbent Assay ; Fluorescein Angiography ; Intravitreal Injections ; Itraconazole/administration & dosage ; Itraconazole/therapeutic use ; Laser Coagulation/adverse effects ; Male ; Rats ; Real-Time Polymerase Chain Reaction ; Vascular Endothelial Growth Factor A/metabolism ; Vascular Endothelial Growth Factor Receptor-2/genetics ; Vascular Endothelial Growth Factor Receptor-2/metabolism |
Chemical Substances | Vascular Endothelial Growth Factor A ; Itraconazole (304NUG5GF4) ; Kdr protein, rat (EC 2.7.10.1) ; Vascular Endothelial Growth Factor Receptor-2 (EC 2.7.10.1) |
Language | English |
Publishing date | 2017 |
Publishing country | United States |
Document type | Journal Article |
ISSN | 1932-6203 |
ISSN (online) | 1932-6203 |
DOI | 10.1371/journal.pone.0180482 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
More links
Kategorien
Order via subito
This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.
Inter-library loan at ZB MED
Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.