Abstract
Age-related macular degeneration (AMD) is a common blinding disease in the western world that is linked to the loss of fenestration in the choriocapillaris that sustains the retinal pigment epithelium and photoreceptors in the back of the eye. Changes in ocular and systemic zinc concentrations have been associated with AMD; therefore, we hypothesized that these changes might be directly involved in fenestrae formation. To test this hypothesis, an endothelial cell (bEND.5) model for fenestrae formation was treated with different concentrations of zinc sulfate (ZnSO4) solution for up to 20 h. Fenestrae were visualized by staining for Plasmalemmal Vesicle Associated Protein-1 (PV-1), the protein that forms the diaphragms of the fenestrated endothelium. Size and distribution were monitored by transmission electron microscopy (TEM). We found that zinc induced the redistribution of PV-1 into areas called sieve plates containing ~70-nm uniform size and typical morphology fenestrae. As AMD is associated with reduced zinc concentrations in the serum and in ocular tissues, and dietary zinc supplementation is recommended to slow disease progression, we propose here that the elevation of zinc concentration may restore choriocapillaris fenestration resulting in improved nutrient flow and clearance of waste material in the retina.
Highlights
Age-related macular degeneration (AMD) is a degenerative disease of the outer retina that leads to irreversible vision loss and legal blindness [1]
BEND.5 cells were maintained in DMEM supplemented with glutamine, pyruvate, 10% fetal calf serum (FCS), antibiotics, non-essential amino acids (NEAA), and β-mercaptoethanol (β-ME)
Deficiencies of zinc have been associated with poor diet and aging
Summary
Age-related macular degeneration (AMD) is a degenerative disease of the outer retina that leads to irreversible vision loss and legal blindness [1]. Pharmacological treatments for AMD delay but do not prevent disease progression, involve invasive procedures, and are costly [2]. Zinc is a ubiquitous trace element present throughout the human body [6]. Many of the functions of zinc are enabled by its ability to interact with amino acids and binding to proteins [7]. One of the highest tissue concentrations of zinc in the human body is found in the retina/choroid complex in the eye [6]. The choriocapillary endothelium enables efficient delivery of oxygen and nutrients and removal of metabolic waste into the peripheral circulation [8]
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