Cargando…

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

PURPOSE: 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 t...

Descripción completa

Detalles Bibliográficos
Autores principales: White, Tomas L., Lewis, Philip, Hayes, Sally, Fergusson, James, Bell, James, Farinha, Luis, White, Nick S., Pereira, Lygia V., Meek, Keith M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Association for Research in Vision and Ophthalmology 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5695733/
https://www.ncbi.nlm.nih.gov/pubmed/28395026
http://dx.doi.org/10.1167/iovs.16-21358
_version_ 1783280352728449024
author White, Tomas L.
Lewis, Philip
Hayes, Sally
Fergusson, James
Bell, James
Farinha, Luis
White, Nick S.
Pereira, Lygia V.
Meek, Keith M.
author_facet White, Tomas L.
Lewis, Philip
Hayes, Sally
Fergusson, James
Bell, James
Farinha, Luis
White, Nick S.
Pereira, Lygia V.
Meek, Keith M.
author_sort White, Tomas L.
collection PubMed
description PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
format Online
Article
Text
id pubmed-5695733
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher The Association for Research in Vision and Ophthalmology
record_format MEDLINE/PubMed
spelling pubmed-56957332017-11-22 The Structural Role of Elastic Fibers in the Cornea Investigated Using a Mouse Model for Marfan Syndrome White, Tomas L. Lewis, Philip Hayes, Sally Fergusson, James Bell, James Farinha, Luis White, Nick S. Pereira, Lygia V. Meek, Keith M. Invest Ophthalmol Vis Sci Cornea PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. The Association for Research in Vision and Ophthalmology 2017-11 /pmc/articles/PMC5695733/ /pubmed/28395026 http://dx.doi.org/10.1167/iovs.16-21358 Text en Copyright 2017 The Authors http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License.
spellingShingle Cornea
White, Tomas L.
Lewis, Philip
Hayes, Sally
Fergusson, James
Bell, James
Farinha, Luis
White, Nick S.
Pereira, Lygia V.
Meek, Keith M.
The Structural Role of Elastic Fibers in the Cornea Investigated Using a Mouse Model for Marfan Syndrome
title The Structural Role of Elastic Fibers in the Cornea Investigated Using a Mouse Model for Marfan Syndrome
title_full The Structural Role of Elastic Fibers in the Cornea Investigated Using a Mouse Model for Marfan Syndrome
title_fullStr The Structural Role of Elastic Fibers in the Cornea Investigated Using a Mouse Model for Marfan Syndrome
title_full_unstemmed The Structural Role of Elastic Fibers in the Cornea Investigated Using a Mouse Model for Marfan Syndrome
title_short The Structural Role of Elastic Fibers in the Cornea Investigated Using a Mouse Model for Marfan Syndrome
title_sort structural role of elastic fibers in the cornea investigated using a mouse model for marfan syndrome
topic Cornea
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5695733/
https://www.ncbi.nlm.nih.gov/pubmed/28395026
http://dx.doi.org/10.1167/iovs.16-21358
work_keys_str_mv AT whitetomasl thestructuralroleofelasticfibersinthecorneainvestigatedusingamousemodelformarfansyndrome
AT lewisphilip thestructuralroleofelasticfibersinthecorneainvestigatedusingamousemodelformarfansyndrome
AT hayessally thestructuralroleofelasticfibersinthecorneainvestigatedusingamousemodelformarfansyndrome
AT fergussonjames thestructuralroleofelasticfibersinthecorneainvestigatedusingamousemodelformarfansyndrome
AT belljames thestructuralroleofelasticfibersinthecorneainvestigatedusingamousemodelformarfansyndrome
AT farinhaluis thestructuralroleofelasticfibersinthecorneainvestigatedusingamousemodelformarfansyndrome
AT whitenicks thestructuralroleofelasticfibersinthecorneainvestigatedusingamousemodelformarfansyndrome
AT pereiralygiav thestructuralroleofelasticfibersinthecorneainvestigatedusingamousemodelformarfansyndrome
AT meekkeithm thestructuralroleofelasticfibersinthecorneainvestigatedusingamousemodelformarfansyndrome
AT whitetomasl structuralroleofelasticfibersinthecorneainvestigatedusingamousemodelformarfansyndrome
AT lewisphilip structuralroleofelasticfibersinthecorneainvestigatedusingamousemodelformarfansyndrome
AT hayessally structuralroleofelasticfibersinthecorneainvestigatedusingamousemodelformarfansyndrome
AT fergussonjames structuralroleofelasticfibersinthecorneainvestigatedusingamousemodelformarfansyndrome
AT belljames structuralroleofelasticfibersinthecorneainvestigatedusingamousemodelformarfansyndrome
AT farinhaluis structuralroleofelasticfibersinthecorneainvestigatedusingamousemodelformarfansyndrome
AT whitenicks structuralroleofelasticfibersinthecorneainvestigatedusingamousemodelformarfansyndrome
AT pereiralygiav structuralroleofelasticfibersinthecorneainvestigatedusingamousemodelformarfansyndrome
AT meekkeithm structuralroleofelasticfibersinthecorneainvestigatedusingamousemodelformarfansyndrome