Lysyl oxidase-like 1 deficiency alters ultrastructural and biomechanical properties of the peripapillary sclera in mice
Lysyl oxidase-like 1 encoded by the LOXL1 gene is a member of the lysyl oxidase family of enzymes that are important in the maintenance of extracellular matrix (ECM)-rich tissue. LOXL1 is important for proper elastic fiber formation and mice lacking LOXL1 (Loxl1−/−) exhibit systemic elastic fiber di...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-12-01
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| Series: | Matrix Biology Plus |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590028522000205 |
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| author | Lauren K. Wareham John Kuchtey Hang-Jing Wu Evan Krystofiak Yusheng Wu Cynthia A. Reinhart-King Rachel W. Kuchtey |
| author_facet | Lauren K. Wareham John Kuchtey Hang-Jing Wu Evan Krystofiak Yusheng Wu Cynthia A. Reinhart-King Rachel W. Kuchtey |
| author_sort | Lauren K. Wareham |
| collection | DOAJ |
| description | Lysyl oxidase-like 1 encoded by the LOXL1 gene is a member of the lysyl oxidase family of enzymes that are important in the maintenance of extracellular matrix (ECM)-rich tissue. LOXL1 is important for proper elastic fiber formation and mice lacking LOXL1 (Loxl1−/−) exhibit systemic elastic fiber disorders, such as pelvic organ prolapse, a phenotype associated with exfoliation syndrome (XFS) in humans. Patients with XFS have a significant risk of developing exfoliation glaucoma (XFG), a severe form of glaucoma, which is a neurodegenerative condition leading to irreversible blindness if not detected and treated in a timely fashion. Although Loxl1−/− mice have been used extensively to investigate mechanisms of pelvic organ prolapse, studies of eyes in those mice are limited and some showed inconsistent ocular phenotypes. In this study we demonstrate that Loxl1−/− mice have significant anterior segment biometric abnormalities which recapitulate some human XFS features. We then focused on the peripapillary sclera (PPS), a critical structure for maintaining optic nerve health. We discovered quantitative and qualitive changes in ultrastructure of PPS, such as reduced elastic fibers, enlarged collagen fibrils, and transformed collagen lamella organization detected by transmission electron microscopy (TEM). Importantly, these changes corelate with altered tissue biomechanics detected by Atomic Force Microscopy (AFM) of PPS in mice. Together, our results support a crucial role for LOXL1 in ocular tissue structure and biomechanics, and Loxl1−/− mice could be a valuable resource for understanding the role of scleral tissue biomechanics in ocular disease. |
| first_indexed | 2024-04-11T05:28:16Z |
| format | Article |
| id | doaj.art-7c4668119b6448e9a94d441e342eee23 |
| institution | Directory Open Access Journal |
| issn | 2590-0285 |
| language | English |
| last_indexed | 2024-04-11T05:28:16Z |
| publishDate | 2022-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Matrix Biology Plus |
| spelling | doaj.art-7c4668119b6448e9a94d441e342eee232022-12-23T04:41:54ZengElsevierMatrix Biology Plus2590-02852022-12-0116100120Lysyl oxidase-like 1 deficiency alters ultrastructural and biomechanical properties of the peripapillary sclera in miceLauren K. Wareham0John Kuchtey1Hang-Jing Wu2Evan Krystofiak3Yusheng Wu4Cynthia A. Reinhart-King5Rachel W. Kuchtey6Vanderbilt Eye Institute, Department of Ophthalmology and Visual Sciences, Vanderbilt University Medical Center, Nashville, TN, USAVanderbilt Eye Institute, Department of Ophthalmology and Visual Sciences, Vanderbilt University Medical Center, Nashville, TN, USAVanderbilt Eye Institute, Department of Ophthalmology and Visual Sciences, Vanderbilt University Medical Center, Nashville, TN, USACell Imaging Shared Resource, Vanderbilt University, Nashville, TN, USADepartment of Biomedical Engineering, Vanderbilt University, Nashville, TN, USADepartment of Biomedical Engineering, Vanderbilt University, Nashville, TN, USAVanderbilt Eye Institute, Department of Ophthalmology and Visual Sciences, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA; Corresponding author at: Vanderbilt Eye Institute, 2311 Pierce Avenue, Nashville, Tennessee 37232, USA.Lysyl oxidase-like 1 encoded by the LOXL1 gene is a member of the lysyl oxidase family of enzymes that are important in the maintenance of extracellular matrix (ECM)-rich tissue. LOXL1 is important for proper elastic fiber formation and mice lacking LOXL1 (Loxl1−/−) exhibit systemic elastic fiber disorders, such as pelvic organ prolapse, a phenotype associated with exfoliation syndrome (XFS) in humans. Patients with XFS have a significant risk of developing exfoliation glaucoma (XFG), a severe form of glaucoma, which is a neurodegenerative condition leading to irreversible blindness if not detected and treated in a timely fashion. Although Loxl1−/− mice have been used extensively to investigate mechanisms of pelvic organ prolapse, studies of eyes in those mice are limited and some showed inconsistent ocular phenotypes. In this study we demonstrate that Loxl1−/− mice have significant anterior segment biometric abnormalities which recapitulate some human XFS features. We then focused on the peripapillary sclera (PPS), a critical structure for maintaining optic nerve health. We discovered quantitative and qualitive changes in ultrastructure of PPS, such as reduced elastic fibers, enlarged collagen fibrils, and transformed collagen lamella organization detected by transmission electron microscopy (TEM). Importantly, these changes corelate with altered tissue biomechanics detected by Atomic Force Microscopy (AFM) of PPS in mice. Together, our results support a crucial role for LOXL1 in ocular tissue structure and biomechanics, and Loxl1−/− mice could be a valuable resource for understanding the role of scleral tissue biomechanics in ocular disease.http://www.sciencedirect.com/science/article/pii/S2590028522000205Lysyl oxidase-like 1Exfoliation glaucomaPeripapillary scleraExtracellular matrixTransmission electron microscopyAtomic force microscopy |
| spellingShingle | Lauren K. Wareham John Kuchtey Hang-Jing Wu Evan Krystofiak Yusheng Wu Cynthia A. Reinhart-King Rachel W. Kuchtey Lysyl oxidase-like 1 deficiency alters ultrastructural and biomechanical properties of the peripapillary sclera in mice Matrix Biology Plus Lysyl oxidase-like 1 Exfoliation glaucoma Peripapillary sclera Extracellular matrix Transmission electron microscopy Atomic force microscopy |
| title | Lysyl oxidase-like 1 deficiency alters ultrastructural and biomechanical properties of the peripapillary sclera in mice |
| title_full | Lysyl oxidase-like 1 deficiency alters ultrastructural and biomechanical properties of the peripapillary sclera in mice |
| title_fullStr | Lysyl oxidase-like 1 deficiency alters ultrastructural and biomechanical properties of the peripapillary sclera in mice |
| title_full_unstemmed | Lysyl oxidase-like 1 deficiency alters ultrastructural and biomechanical properties of the peripapillary sclera in mice |
| title_short | Lysyl oxidase-like 1 deficiency alters ultrastructural and biomechanical properties of the peripapillary sclera in mice |
| title_sort | lysyl oxidase like 1 deficiency alters ultrastructural and biomechanical properties of the peripapillary sclera in mice |
| topic | Lysyl oxidase-like 1 Exfoliation glaucoma Peripapillary sclera Extracellular matrix Transmission electron microscopy Atomic force microscopy |
| url | http://www.sciencedirect.com/science/article/pii/S2590028522000205 |
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