Cargando…

Collagen V insufficiency in a mouse model for Ehlers Danlos-syndrome affects viscoelastic biomechanical properties explaining thin and brittle corneas

Ehlers–Danlos syndrome (EDS) is a genetic disease leading to abnormalities in mechanical properties of different tissues. Here we quantify corneal biomechanical properties in an adult classic EDS mouse model using two different measurement approaches suited for murine corneal mechanical characteriza...

Descripción completa

Detalles Bibliográficos
Autores principales: Kling, Sabine, Torres-Netto, Emilio A., Abdshahzadeh, Hormoz, Espana, Edgar M., Hafezi, Farhad
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8405695/
https://www.ncbi.nlm.nih.gov/pubmed/34462473
http://dx.doi.org/10.1038/s41598-021-96775-w
_version_ 1783746380878053376
author Kling, Sabine
Torres-Netto, Emilio A.
Abdshahzadeh, Hormoz
Espana, Edgar M.
Hafezi, Farhad
author_facet Kling, Sabine
Torres-Netto, Emilio A.
Abdshahzadeh, Hormoz
Espana, Edgar M.
Hafezi, Farhad
author_sort Kling, Sabine
collection PubMed
description Ehlers–Danlos syndrome (EDS) is a genetic disease leading to abnormalities in mechanical properties of different tissues. Here we quantify corneal biomechanical properties in an adult classic EDS mouse model using two different measurement approaches suited for murine corneal mechanical characterization and relate differences to stromal structure using Second Harmonic Generation (SHG) microscopy. Quasi-static Optical Coherence Elastography (OCE) was conducted non-invasively during ambient pressure modulation by − 3 mmHg. 2D-extensometry measurements was conducted invasively consisting of a pre-conditioning cycle, a stress-relaxation test and a rupture test. In a total of 28 eyes from a Col5a1(+/−) mouse model and wild-type C57BL/6 littermates (wt), Col5a1(+/−) corneas were thinner when compared to wt, (125 ± 11 vs 148 ± 10 μm, respectively, p < 0.001). Short-term elastic modulus was significantly increased in OCE (506 ± 88 vs 430 ± 103 kPa, p = 0.023), and the same trend was observed in 2D-extensometry (30.7 ± 12.1 kPa vs 21.5 ± 5.7, p = 0.057). In contrast, in stress relaxation tests, Col5a1(+/−) corneas experienced a stronger relaxation (55% vs 50%, p = 0.01). SHG microscopy showed differences in forward and backward scattered signal indicating abnormal collagen fibrils in Col5a1(+/−) corneas. We propose that disturbed collagen fibril structure in Col5a1(+/−) corneas affects the viscoelastic properties. Results presented here support clinical findings, in which thin corneas with global ultrastructural alterations maintain a normal corneal shape.
format Online
Article
Text
id pubmed-8405695
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-84056952021-09-01 Collagen V insufficiency in a mouse model for Ehlers Danlos-syndrome affects viscoelastic biomechanical properties explaining thin and brittle corneas Kling, Sabine Torres-Netto, Emilio A. Abdshahzadeh, Hormoz Espana, Edgar M. Hafezi, Farhad Sci Rep Article Ehlers–Danlos syndrome (EDS) is a genetic disease leading to abnormalities in mechanical properties of different tissues. Here we quantify corneal biomechanical properties in an adult classic EDS mouse model using two different measurement approaches suited for murine corneal mechanical characterization and relate differences to stromal structure using Second Harmonic Generation (SHG) microscopy. Quasi-static Optical Coherence Elastography (OCE) was conducted non-invasively during ambient pressure modulation by − 3 mmHg. 2D-extensometry measurements was conducted invasively consisting of a pre-conditioning cycle, a stress-relaxation test and a rupture test. In a total of 28 eyes from a Col5a1(+/−) mouse model and wild-type C57BL/6 littermates (wt), Col5a1(+/−) corneas were thinner when compared to wt, (125 ± 11 vs 148 ± 10 μm, respectively, p < 0.001). Short-term elastic modulus was significantly increased in OCE (506 ± 88 vs 430 ± 103 kPa, p = 0.023), and the same trend was observed in 2D-extensometry (30.7 ± 12.1 kPa vs 21.5 ± 5.7, p = 0.057). In contrast, in stress relaxation tests, Col5a1(+/−) corneas experienced a stronger relaxation (55% vs 50%, p = 0.01). SHG microscopy showed differences in forward and backward scattered signal indicating abnormal collagen fibrils in Col5a1(+/−) corneas. We propose that disturbed collagen fibril structure in Col5a1(+/−) corneas affects the viscoelastic properties. Results presented here support clinical findings, in which thin corneas with global ultrastructural alterations maintain a normal corneal shape. Nature Publishing Group UK 2021-08-30 /pmc/articles/PMC8405695/ /pubmed/34462473 http://dx.doi.org/10.1038/s41598-021-96775-w Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Kling, Sabine
Torres-Netto, Emilio A.
Abdshahzadeh, Hormoz
Espana, Edgar M.
Hafezi, Farhad
Collagen V insufficiency in a mouse model for Ehlers Danlos-syndrome affects viscoelastic biomechanical properties explaining thin and brittle corneas
title Collagen V insufficiency in a mouse model for Ehlers Danlos-syndrome affects viscoelastic biomechanical properties explaining thin and brittle corneas
title_full Collagen V insufficiency in a mouse model for Ehlers Danlos-syndrome affects viscoelastic biomechanical properties explaining thin and brittle corneas
title_fullStr Collagen V insufficiency in a mouse model for Ehlers Danlos-syndrome affects viscoelastic biomechanical properties explaining thin and brittle corneas
title_full_unstemmed Collagen V insufficiency in a mouse model for Ehlers Danlos-syndrome affects viscoelastic biomechanical properties explaining thin and brittle corneas
title_short Collagen V insufficiency in a mouse model for Ehlers Danlos-syndrome affects viscoelastic biomechanical properties explaining thin and brittle corneas
title_sort collagen v insufficiency in a mouse model for ehlers danlos-syndrome affects viscoelastic biomechanical properties explaining thin and brittle corneas
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8405695/
https://www.ncbi.nlm.nih.gov/pubmed/34462473
http://dx.doi.org/10.1038/s41598-021-96775-w
work_keys_str_mv AT klingsabine collagenvinsufficiencyinamousemodelforehlersdanlossyndromeaffectsviscoelasticbiomechanicalpropertiesexplainingthinandbrittlecorneas
AT torresnettoemilioa collagenvinsufficiencyinamousemodelforehlersdanlossyndromeaffectsviscoelasticbiomechanicalpropertiesexplainingthinandbrittlecorneas
AT abdshahzadehhormoz collagenvinsufficiencyinamousemodelforehlersdanlossyndromeaffectsviscoelasticbiomechanicalpropertiesexplainingthinandbrittlecorneas
AT espanaedgarm collagenvinsufficiencyinamousemodelforehlersdanlossyndromeaffectsviscoelasticbiomechanicalpropertiesexplainingthinandbrittlecorneas
AT hafezifarhad collagenvinsufficiencyinamousemodelforehlersdanlossyndromeaffectsviscoelasticbiomechanicalpropertiesexplainingthinandbrittlecorneas