Lactoferrin Has a Therapeutic Effect HIF Inhibition in a Murine Model of Choroidal Neovascularization.

BACKGROUND

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. 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.

METHODS

HIF inhibitory effects of lactoferrin were evaluated using a luciferase assay and western blotting . The quantified volume of choroidal neovascularization (CNV) induced by laser irradiation was compared with oral lactoferrin administration or conditional tissue specific knockout mice.

RESULTS

Lactoferrin administration showed a significant HIF inhibitory effect in the retinal neuronal cells. Oral administration of lactoferrin or conditional gene deletion significantly reduced CNV volume compared to controls.

CONCLUSIONS

Lactoferrin has a therapeutic effect in a laser CNV model by suppressing the retinal HIF activity.