Microfibril-Associated Glycoprotein-1 Controls Human Ciliary Zonule Development <i>In Vitro</i>

Abstract

The ciliary zonule in the eye, also known as Zinn’s zonule, is composed of oxytalan fibers, which are bundles of microfibrils consisting mainly of fibrillin-1. However, it is still unclear which of the microfibril-associated molecules present in the ciliary zonule controls oxytalan fibers. Microfibril-associated glycoprotein-1 (MAGP-1) is the only microfibril-associated molecule identified in the human ciliary zonule. In the present study, we used siRNA against MAGP-1 in cultures of human non-pigmented ciliary epithelial cells to examine the extracellular deposition and appearance of fibrillin-1 employing Western blotting and immunofluorescence. MAGP-1 suppression led to a reduction of fibrillin-1 deposition. Immunofluorescence also confirmed that RNAi-mediated down-regulation of MAGP-1 led to suppression of fiber development. These results suggest that MAGP-1 plays a crucial role in the extracellular deposition of fibrillin-1 during formation of the human ciliary zonule.

Induction of Immune Surveillance of the Dysmorphogenic Lens

“…We were therefore curious whether this system extends to the lens. We co-immunostained sections from adult eyes of normal and N-cad Δlens mice using antibodies to lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1), which is expressed by lymphatic endothelial cells and typically used to detect lymphatic vessels 58 , 59 , and MAGP1, a microfibrillar protein component of the ciliary zonules, the suspensory ligaments that connect the lens to the ciliary body 60 – 62 . We discovered that LYVE-1 positive labeling was closely aligned along MAGP1-positive suspensory ligaments in lenses from both wildtype and N-cad Δlens eyes (Fig.…”

MFAP2 promotes epithelial&ndash;mesenchymal transition in gastric cancer cells by activating TGF-&beta;/SMAD2/3 signaling pathway

“… 8 , 9 There is a fibrillin-binding domain in the carboxyl-terminal region of MFAP2, which contains 13 cysteine residues and binds MFAP2 to the extracellular matrix and an acidic amino-terminal region containing a growth factor interaction motif capable of interacting with the active form of transforming growth factor beta (TGF-β), but not with the latent form of the growth factor. 10 , 11 MFAP2 plays an important role in the extracellular deposition of fibrillin-1 during development of the human ciliary zonule, 12 and an in vivo study found that MFAP2 plays a key role in hemostasis and thrombosis because MFAP2-deficient mice showed delayed thrombotic occlusion of the carotid artery following injury, prolonged bleeding, and lower platelet number. 13 …”

Nanophthalmos-AssociatedMYRFGene Mutation Causes Ciliary Zonule Defects in Mice

“…The main role of zonules is to maintain the lens in the center of the visual pathway and transmit contraction forces from ciliary bodies to the lens for accommodation. 26,27 Zonules can be classified into three subgroups: anterior, equatorial, and posterior parts based on the attachment point of these fibers on the lens. 28 Reduction in tensile strength of ciliary zonules or rupture of any fibers in any subgroup can weaken traction force to the lens.…”