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Lauren Beene, Lauren Wang, Robert Mecham, Dieter Reinhardt, Elias Traboulsi, Suneel Apte; Fibrillin-2 is a component of the mouse zonule. Invest. Ophthalmol. Vis. Sci. 2013;54(15):466.
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© ARVO (1962-2015); The Authors (2016-present)
Fibrillins are the major constituent of microfibrils. FBN1 mutations lead to Marfan syndrome and deficiency of the microfibril-composed ciliary zonule, causing ectopia lentis. Analysis of Fbn1-null mouse eyes unexpectedly demonstrated an apparently intact zonule, whose composition was analyzed. The authors investigated microfibril biogenesis in wild-type (WT), Fbn1- and Fbn2-null fibroblasts.
The ciliary zonule of WT and Fbn1-null mice (mgN), as well as normal rat, bovine and human eyes was stained by immunofluorescence using fibrillin-1 and fibrillin-2 antibodies. Antibody specificity was demonstrated by staining Fbn1-null and Fbn2- null control tissues. The zonule in Fbn1-null mouse eyes was examined by transmission electron microscopy (TEM). Microfibril biogenesis in WT, Fbn1-null and Fbn2-null mouse fibroblasts was evaluated by immunofluorescence.
Contrary to expectation, a zonule was evident in Fbn1-null mouse eyes. TEM confirmed this finding and showed microfibrils adjacent to the ciliary body. Immunofluorescence demonstrated fibrillin-2 in the zonule of WT and Fbn1-null mouse, as well as rat, contrasting with human and bovine. Analysis of microfibril biogenesis in fibroblasts demonstrated when both fibrillin-1 and fibrillin-2 were present, heterotypic microfibrils formed. Fibrillin-2 microfibrils formed in Fbn1-null cultures, and vice versa. Fibrillin-2 assembly in Fbn1-null and WT fibroblasts was initiated by punctate deposits, which elongated to form microfibrils. In absence of exogenous fibronectin, or in presence of fibronectin assembly inhibitor, FUD, fibrillin-2 assembly was reduced.
The presence of fibrillin-2 in the mouse and rat zonule and an intact zonule in Fbn1-null mice limits the utility of these rodents for studying ocular manifestations of Marfan syndrome. These studies suggest microfibril composition depends on the levels of fibrillin isoform expression and the fibroblast assembly mechanism is not selective. Like fibrillin-1, assembly of fibrillin-2 microfibrils is dependent on fibronectin. This raises the intriguing possibility that zonules could be generated or maintained in Marfan syndrome by expressing fibrillin-2 in the ciliary body.
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