The Structural Role of Elastic Fibers in the Cornea Investigated Using a Mouse Model for Marfan Syndrome

• Published in: Investigative ophthalmology & visual science 2017-04, Vol.58 (4), p.2106-2116
• Main Authors: White, Tomas L, Lewis, Philip, Hayes, Sally, Fergusson, James, Bell, James, Farinha, Luis, White, Nick S, Pereira, Lygia V, Meek, Keith M
• Format: Article
• Language: English
• Subjects: Animals; Cornea; Cornea - metabolism; Cornea - ultrastructure; Disease Models, Animal; DNA - genetics; DNA Mutational Analysis; Elastic Tissue - ultrastructure; Fibrillin-1 - genetics; Fibrillin-1 - metabolism; Marfan Syndrome - diagnosis; Marfan Syndrome - genetics; Marfan Syndrome - metabolism; Mice; Mice, Mutant Strains; Microfibrils - ultrastructure; Microscopy, Electron, Scanning; Microscopy, Electron, Transmission; Mutation; Tomography, Optical Coherence
• ISSN: 1552-5783; 0146-0404; 1552-5783
• DOI: 10.1167/iovs.16-21358

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.