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Effect of lutein and antioxidant supplementation on VEGF expression, MMP-2 activity, and ultrastructural alterations
Patricia Fernández-Robredo1, Luis M Sádaba, Angel Salinas-Alamán
1Experimental Ophthalmology Laboratory, Clínica Universidad de Navarra, School of Medicine, University of Navarra, ES-31008 Pamplona, Spain.
Abstract:
Oxidative stress is involved in the pathogenesis of several diseases such as atherosclerosis and age-related macular degeneration (AMD). ApoE-deficient mice (apoE(-/-)) are a well-established model of genetic hypercholesterolemia and develop retinal alterations similar to those found in humans with AMD. Thus supplementation with lutein or multivitamin plus lutein and glutathione complex (MV) could prevent the onset of these alterations. ApoE(-/-) mice (n = 40, 3 months old) were treated daily for 3 months with lutein (AE-LUT) or MV (two doses): AE-MV15 (15 mg/kg/day) and AE-MV50 (50 mg/kg/day) and were compared to controls with vehicle (AE-C). Wild-type mice (n = 10) were also used as control (WT-C). ApoE(-/-) mice showed higher retinal lipid peroxidation and increased VEGF expression and MMP-2 activity, associated with ultrastructural alterations such as basal laminar deposits, vacuoles, and an increase in Bruch's membrane thickness. While lutein alone partially prevented the alterations observed in apoE(-/-) mice, MV treatment substantially reduced VEGF levels and MMP-2 activity and ameliorated the retinal morphological alterations. These results suggest that oxidative stress in addition to an increased expression and activity of proangiogenic factors could participate in the onset or development of retinal alterations of apoE(-/-) mice. Moreover, these changes could be prevented by efficient antioxidant treatments.
Insights
Multivitamin (MV) and lutein supplementation can prevent retinal damage in a mouse model of high cholesterol. MV treatment significantly reduced oxidative stress and vascular growth factors, improving retinal structure.
Area of Science:
- Ophthalmology
- Cardiovascular Biology
- Nutritional Science
Background:
- Oxidative stress and vascular changes contribute to age-related macular degeneration (AMD).
- ApoE-deficient mice (apoE(-/-)) exhibit hypercholesterolemia and retinal alterations mimicking human AMD.
- Antioxidant and multivitamin therapies are explored for preventing such retinal damage.
Purpose of the Study:
- To investigate the protective effects of lutein and a multivitamin complex (MV) against retinal alterations in apoE(-/-) mice.
- To assess the role of oxidative stress and proangiogenic factors in AMD-like retinal pathology.
Main Methods:
- ApoE(-/-) mice were treated with lutein (AE-LUT) or two doses of MV (AE-MV15, AE-MV50) for 3 months.
- Retinal lipid peroxidation, VEGF expression, and MMP-2 activity were measured.
- Ultrastructural analysis examined Bruch's membrane thickness, basal laminar deposits, and vacuoles.
Main Results:
- ApoE(-/-) mice displayed increased retinal lipid peroxidation, VEGF, and MMP-2 activity, with significant ultrastructural damage.
- Lutein offered partial protection against these retinal alterations.
- MV treatment substantially decreased VEGF and MMP-2 levels and ameliorated morphological damage.
Conclusions:
- Oxidative stress and proangiogenic factors are implicated in the retinal pathology of apoE(-/-) mice.
- Antioxidant treatments, particularly the multivitamin complex, show potential in preventing AMD-like retinal changes.
