Abstract
BackgroundLactoferrin, a type of glycoprotein, is contained in exocrine fluids such as tears, breast milk, sweat, and saliva, and is known to have anti-microbial, antioxidant, and anti-cancer effects. In the ophthalmological field, topical administration of lactoferrin has been reported to have a therapeutic effect in a murine dry eye model. Hypoxia-inducible factor (HIF) regulates various gene expressions under hypoxia, including vascular endothelial growth factor (VEGF), and is considered as an alternative target for neovascular ocular diseases such as age-related macular degeneration (AMD). We previously screened natural products and identified lactoferrin as a novel HIF inhibitor. In this study, we confirmed that lactoferrin has an HIF inhibitory effect and a therapeutic effect in a murine model of neovascular AMD.MethodsHIF inhibitory effects of lactoferrin were evaluated using a luciferase assay and western blotting in vitro. The quantified volume of choroidal neovascularization (CNV) induced by laser irradiation was compared with oral lactoferrin administration or conditional tissue specific Hif1a knockout mice.ResultsLactoferrin administration showed a significant HIF inhibitory effect in the retinal neuronal cells. Oral administration of lactoferrin or conditional Hif1a gene deletion significantly reduced CNV volume compared to controls.ConclusionsLactoferrin has a therapeutic effect in a laser CNV model by suppressing the retinal HIF activity.
Highlights
Lactoferrin, a type of glycoprotein, is contained in exocrine fluids such as nasal exudate, bronchial mucus, breast milk, tears, sweat, and saliva (Iigo et al, 2009)
Hypoxia-inducible factor (HIF) Activation Was Suppressed by Lactoferrin Administration in a Luciferase Assay
Lactoferrin showed an HIF inhibitory effect compared with the control group in ARPE19 cells (Figure 1A) and 661W cells (Figure 1B)
Summary
Lactoferrin, a type of glycoprotein, is contained in exocrine fluids such as nasal exudate, bronchial mucus, breast milk, tears, sweat, and saliva (Iigo et al, 2009). Lactoferrin is known to have several biological functions, including antioxidant, anti-microbial, and anti-cancer effects (Kanwar et al, 2015). Lactoferrin eye drops have been reported to have a therapeutic effect in a murine dry eye model by suppressing oxidative stress (Higuchi et al, 2012; Higuchi et al, 2016). Lactoferrin, a type of glycoprotein, is contained in exocrine fluids such as tears, breast milk, sweat, and saliva, and is known to have anti-microbial, antioxidant, and anti-cancer effects. Topical administration of lactoferrin has been reported to have a therapeutic effect in a murine dry eye model.
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