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Nonselective assembly of fibrillin 1 and fibrillin 2 in the rodent ocular zonule and in cultured cells: implications for Marfan syndrome.

Abstract：

PURPOSE:Fibrillins are the major constituent of tissue microfibrils, which form the ocular zonule. In Marfan syndrome (MFS), FBN1 mutations lead to ectopia lentis. The goal of this work was to investigate zonule composition and formation in fibrillin-deficient and wild-type mice. METHODS:Immunofluorescence staining of eyes from wild-type, Fbn1-deficient, and Fbn2-deficient mice, as well as other species, was performed using monospecific fibrillin 1 and fibrillin 2 antibodies. The zonule of Fbn1-deficient and Fbn2-deficient mice was studied by electron microscopy. Microfibril formation in vitro was evaluated by immunofluorescence microscopy of cultured nonpigmented ciliary epithelial cells and fibroblasts. RESULTS:A zonule was present in both Fbn1-deficient and Fbn2-deficient mouse eyes. Immunofluorescence demonstrated that the zonule of Fbn1-deficient mice, wild-type mice, rats, and hamsters contained fibrillin 2. The zonule of Fbn2(-/-) mice contained fibrillin 1. Fibrillin 1 and fibrillin 2 colocalized in microfibrils formed in human nonpigmented ciliary epithelium cultures. Like fibrillin 1, fibrillin 2 microfibril assembly was fibronectin dependent and initiated by cell surface punctate deposits that elongated to form microfibrils. CONCLUSIONS:These data suggest that fibrillin 1 assembly and fibrillin 2 assembly share similar mechanisms. Microfibril composition depends substantially on the local levels of fibrillin isoforms and is not highly selective in regard to the isoform. This raises the intriguing possibility that the zonule could be strengthened in MFS by inducing fibrillin 2 expression in ciliary epithelium. The presence of fibrillin 2 in the murine zonule and an intact zonule in Fbn1-knockout mice may limit the utility of rodent models for studying ectopia lentis in MFS.

journal_name

Invest Ophthalmol Vis Sci

journal_title

Investigative ophthalmology & visual science

authors

Beene LC,Wang LW,Hubmacher D,Keene DR,Reinhardt DP,Annis DS,Mosher DF,Mecham RP,Traboulsi EI,Apte SS

doi

10.1167/iovs.13-13121

subject

Has Abstract

pub_date

2013-12-23 00:00:00

pages

8337-44

issue

eissn

0146-0404

issn

1552-5783

pii

iovs.13-13121

journal_volume

pub_type

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Nonselective assembly of fibrillin 1 and fibrillin 2 in the rodent ocular zonule and in cultured cells: implications for Marfan syndrome.