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Mari Ibuki, Chiho Shoda, Yukihiro Miwa, Kazuo Tsubota, Toshihide Kurihara; Garcinia extract inhibiting HIF suppresses laser-induced CNV in mice. Invest. Ophthalmol. Vis. Sci. 2019;60(9):1255.
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Neovascular ocular diseases such as diabetic retinopathy and exudative age-related macular degeneration are the leading causes of blindness characterized with pathological angiogenesis in the retina. Although anti-vascular endothelial growth factor (VEGF) therapy has given a potent therapeutic effect against those diseases, there is a possibility of chorioretinal atrophy and systemic adverse events due to long-term robust VEGF antagonism. We have been focusing on hypoxia-inducible factor (HIF) regulating VEGF transcription, and have reported suppressive effects of HIF inhibition against ocular phenotypes in animal models. On the other hands, many of known HIF inhibitors are categorized as anticancer drugs, and systemic side effects are concerned for clinical use. In this study, we explored food ingredients that have HIF inhibitory effects and verified their effects in an animal model of choroidal neovascularization (CNV).
Luciferase was stably transfected on the downstream of the HIF response sequence in the murine retinal cone cell line (661 W). Food ingredients were screened with the transfected cell line 24 hours after administration of 200μM cobalt chloride. 4-week-old male C57BL6/J mice were orally administered the identified substance for total 49 days. CNV was induced by laser irradiation on the day 42 of administration. The CNV volume was quantified by wholemount isolectin-IB4 staining 7 days after irradiation.
We screened 238 types of materials derived from food ingredients, and identified 10 types of substances as HIF inhibitors. Among those identified HIF inhibitors, garcinia extract was orally administered (30 mg / kg / day) to the laser-induced CNV model mice. As a result, the volume of CNV was significantly (p <0.05) decreased in the group treated with garcinia extract (154 ± 81 μm3) compared to the control group (377 ± 296 μm3).
As a novel HIF inhibitor, garcinia extract showed a therapeutic effect on murine laser-induced CNV model.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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