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Intravitreal itraconazole inhibits laser-induced choroidal neovascularization in rats.
PLoS One. 2017; 12(6):e0180482.Plos

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.

Authors+Show Affiliations

Medical Research Institute, Department of Ophthalmology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Republic of Korea.Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Republic of Korea.Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Republic of Korea.Department of Ophthalmology, Seoul National University College of Medicine, Seoul, Republic of Korea.Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Republic of Korea.Department of Pathology, Yonsei University College of Medicine, Seoul, Republic of Korea.Medical Research Institute, Department of Ophthalmology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Republic of Korea.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28666022

Citation

Bae, Jeong Hun, et al. "Intravitreal Itraconazole Inhibits Laser-induced Choroidal Neovascularization in Rats." PloS One, vol. 12, no. 6, 2017, pp. e0180482.
Bae JH, Hwang AR, Kim CY, et al. Intravitreal itraconazole inhibits laser-induced choroidal neovascularization in rats. PLoS One. 2017;12(6):e0180482.
Bae, J. H., Hwang, A. R., Kim, C. Y., Yu, H. G., Koh, H. J., Yang, W. I., Chang, H. R., & Lee, S. C. (2017). Intravitreal itraconazole inhibits laser-induced choroidal neovascularization in rats. PloS One, 12(6), e0180482. https://doi.org/10.1371/journal.pone.0180482
Bae JH, et al. Intravitreal Itraconazole Inhibits Laser-induced Choroidal Neovascularization in Rats. PLoS One. 2017;12(6):e0180482. PubMed PMID: 28666022.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Intravitreal itraconazole inhibits laser-induced choroidal neovascularization in rats. AU - Bae,Jeong Hun, AU - Hwang,Ah Reum, AU - Kim,Chan Yun, AU - Yu,Hyeong Gon, AU - Koh,Hyoung Jun, AU - Yang,Woo Ick, AU - Chang,Hae Ran, AU - Lee,Sung Chul, Y1 - 2017/06/30/ PY - 2017/03/24/received PY - 2017/06/15/accepted PY - 2017/7/1/entrez PY - 2017/7/1/pubmed PY - 2017/10/7/medline SP - e0180482 EP - e0180482 JF - PloS one JO - PLoS One VL - 12 IS - 6 N2 - 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. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/28666022/Intravitreal_itraconazole_inhibits_laser_induced_choroidal_neovascularization_in_rats_ L2 - https://dx.plos.org/10.1371/journal.pone.0180482 DB - PRIME DP - Unbound Medicine ER -