title: The Structural Role of Elastic Fibers in the Cornea Investigated Using a Mouse Model for Marfan Syndrome.
abstract: The presence of fibrillin-rich elastic fibers in the cornea has been overlooked in recent years. The aim of the current study was to elucidate their functional role using a mouse model for Marfan syndrome, defective in fibrillin-1, the major structural component of the microfibril bundles that constitute most of the elastic fibers.
  
  
  
  Mouse corneas were obtained from animals with a heterozygous fibrillin-1 mutation (Fbn1+/-) and compared to wild type controls. Corneal thickness and radius of curvature were calculated using optical coherence tomography microscopy. Elastic microfibril bundles were quantified and visualized in three-dimensions using serial block face scanning electron microscopy. Transmission electron microscopy was used to analyze stromal ultrastructure and proteoglycan distribution. Center-to-center average interfibrillar spacing was determined using x-ray scattering.
  
  
  
  Fbn1+/- corneas were significantly thinner than wild types and displayed a higher radius of curvature. In the Fbn1+/- corneas, elastic microfibril bundles were significantly reduced in density and disorganized compared to wild-type controls, in addition to containing a higher average center-to-center collagen interfibrillar spacing in the center of the cornea. No other differences were detected in stromal ultrastructure or proteoglycan distribution between the two groups. Proteoglycan side chains appeared to colocalize with the microfibril bundles.
  
  
  
  Elastic fibers have an important, multifunctional role in the cornea as highlighted by the differences observed between Fbn1+/- and wild type animals. We contend that the presence of normal quantities of structurally organized elastic fibers are required to maintain the correct geometry of the cornea, which is disrupted in Marfan syndrome.
authors.affiliation: Structural Biophysics Research Group, School of Optometry and Vision Sciences, Cardiff University, Maindy Road, Cardiff, United Kingdom.
authors.forename: Tomas L
authors.initials: TL
authors.lastname: White
authors.affiliation: Structural Biophysics Research Group, School of Optometry and Vision Sciences, Cardiff University, Maindy Road, Cardiff, United Kingdom.
authors.forename: Philip
authors.initials: P
authors.lastname: Lewis
authors.affiliation: Structural Biophysics Research Group, School of Optometry and Vision Sciences, Cardiff University, Maindy Road, Cardiff, United Kingdom.
authors.forename: Sally
authors.initials: S
authors.lastname: Hayes
authors.affiliation: Vision Science Bioimaging Labs, School of Optometry and Vision Sciences, Cardiff University, Cardiff, United Kingdom.
authors.forename: James
authors.initials: J
authors.lastname: Fergusson
authors.affiliation: Structural Biophysics Research Group, School of Optometry and Vision Sciences, Cardiff University, Maindy Road, Cardiff, United Kingdom.
authors.forename: James
authors.initials: J
authors.lastname: Bell
authors.affiliation: Department of Genetics and Evolutionary Biology, University of São Paulo, Rua do Matão, São Paulo, Brazil.
authors.forename: Luis
authors.initials: L
authors.lastname: Farinha
authors.affiliation: Vision Science Bioimaging Labs, School of Optometry and Vision Sciences, Cardiff University, Cardiff, United Kingdom.
authors.forename: Nick S
authors.initials: NS
authors.lastname: White
authors.affiliation: Department of Genetics and Evolutionary Biology, University of São Paulo, Rua do Matão, São Paulo, Brazil.
authors.forename: Lygia V
authors.initials: LV
authors.lastname: Pereira
authors.affiliation: Structural Biophysics Research Group, School of Optometry and Vision Sciences, Cardiff University, Maindy Road, Cardiff, United Kingdom.
authors.forename: Keith M
authors.initials: KM
authors.lastname: Meek
mesh_terms: D000818:Animals; D003315:Cornea / Q000378:metabolism / Q000648:ultrastructure*; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis; D004195:Disease Models, Animal; D004547:Elastic Tissue / Q000648:ultrastructure*; D000071838:Fibrillin-1 / Q000235:genetics / Q000378:metabolism; D008382:Marfan Syndrome / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D020894:Microfibrils / Q000648:ultrastructure; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D009154:Mutation; D041623:Tomography, Optical Coherence; D054392:Adipokines
chemical_list: D004247:DNA; D000071838:Fibrillin-1; C000605724:Fbn1 protein, mouse; D054392:Adipokines