Lactoferrin Reduces Chorioretinal Damage in the Murine Laser Model of Choroidal Neovascularization

Abstract

Purpose: To determine whether lactoferrin, specifically endogenous mouse lactoferrin and exogenous intraperitoneal lactoferrin treatment, plays a role in reducing the chorioretinal damage in the laser-induced model of choroidal neovascularization.

Materials and methods: Four 532-nm argon laser spots were placed between the retinal vessels of each eye. At Day 7, Fluorescein Angiography was performed to grade the lesions. The mice were perfused with fluorescein-labeled tomato lectin and sacrificed. The retinal pigment epithelium-choroid-sclera complex was flat-mounted and analyzed with a confocal microscope to measure the volume of the lesions. The effect of endogenous lactoferrin was studied by comparing lactoferrin knockout and wild-type (WT) mice. The effect of exogenous lactoferrin treatment was studied by comparing lactoferrin knockout and WT mice treated with lactoferrin for seven days to their respective controls.

Results: Lactoferrin knockout mice demonstrated 47% larger lesion volumes than WT mice (p < 0.001). Intraperitoneal treatment with Lactoferrin reduced the lesion volume in Lactoferrin knockout mice by 26% (p < 0.04). Regarding the fluorescein angiography, lesions indicating the greatest damage (grade 2B) occurred more frequently in control lactoferrin knockout mice compared with control WT mice (16% versus 5%). Intraperitoneal treatment with Lactoferrin reduced the grade 2B lesions from16% to 2% in Lactoferrin knockout mice.

Conclusion: The endogenous lactoferrin present in WT mice appears to reduce the choroidal neovascularization in the laser-induced choroidal neovascularization model in mice. Treatment with exogenous lactoferrin is capable of reducing the choroidal neovascularization in lactoferrin knockout mice but does not add a significant protective effect to WT.

Keywords:

• Angiogenesis
• choroidal neovascularization
• lactoferrin
• macular degeneration

Acknowledgments

The authors thank Drs David Briles and Brandon Hatcher of the University of Texas and Dr. Pauline Ward of the University of Alabama for generously providing lactoferrin knockout mice for this study. Thanks to Drs Demetrios Vavvas, George Trichonas, Aris Thanos and Akrivi Manola for prior preliminary data published electronically in the E-abstract 48, at IVOS 2009; 50:ARVO.

Declaration of interest

No author has a financial or proprietary interest in any material or method mentioned.

Funding was obtained from University of Minnesota Foundation, Minnesota Lions Vision Foundation, and an Anonymous Donor to the Department of Ophthalmology and Visual Neurosciences for AMD research.

An unrestricted grant to the Department of Ophthalmology and Visual Neurosciences from the Research to Prevent Blindness (RPB), New York, NY, USA.

Travel support was obtained from the Vitreo Retinal Surgery Foundation, Minneapolis, MN, (LDD).