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Wendell Jones, Steven Bassnett; The role of fibrillin-1 in ciliary zonule synthesis and lens growth. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3067.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: The purpose of this study was to test the role of fibrillin-1 (FBN-1) in ciliary zonule synthesis and lens growth. FBN-1, a large extracellular matrix glycoprotein, is the principal component of the ciliary zonule. In humans, mutations in FBN-1 are associated with syndromic disorders in which the growth of the lens is often affected.
Methods: Fbn-1-null mice die shortly after birth, making it difficult to study the role of Fbn-1 in ocular development. Therefore, we generated a FBN-1 conditional knockout (cKO) mouse by crossing Fbn-1flox/flox mice with Pax6αCRE, a line in which CRE-recombinase is expressed in the inner layer of the optic cup (including the non-pigmented ciliary epithelium (NPCE)). To identify CRE-expressing cells, Fbn-1flox/flox; Pax6αCRE +/- mice were crossed onto an mT/mG reporter background. The organization of the ciliary zonule was visualized using antibodies against FBN-1 or microfibril associated glycoprotein-1 (MAGP1) and imaged by confocal microscopy.
Results: CRE expression was restricted to the nasal and temporal regions of the NPCE. In CRE-expressing areas, posterior zonular fibers were absent and the remaining anterior fibers were unusually long. The organization of zonular fibers in CRE-negative regions was similar to wildtype. In cKO mice, the zonular fibers progressively ruptured, resulting in an ectopia lentis phenotype by 2 months of age. Fbn-1 cKO lenses were slightly smaller than controls. Three dimensional reconstructions of cKO lenses revealed that the density of epithelial cells was approximately two fold greater than in controls and that the orderly differentiation of fiber cells at the lens equator was disrupted.
Conclusion: A cKO mouse model was used to disrupt Fbn-1 expression in segments of the NPCE. Our data suggest that FBN-1 is not essential for zonule synthesis but that, in its absence, zonular fibers eventually break, resulting in lens dislocation. Alterations in epithelial population dynamics and fiber differentiation observed in cKO mice imply a role for FBN1 in the control of lens growth.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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