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Decorin regulates collagen fibrillogenesis during corneal wound healing in mouse in vivo.
Exp Eye Res. 2022 03; 216:108933.EE

Abstract

A characteristic rigid spatial arrangement of collagen fibrils in the stroma is critical for corneal transparency. This unique organization of collagen fibrils in corneal stroma can be impacted by the presence and interactions of proteoglycans and extracellular matrix (ECM) proteins in a corneal microenvironment. Earlier studies revealed that decorin, a leucine-rich proteoglycan in stroma, regulates keratocyte-collagen matrix assembly and wound healing in the cornea. This study investigated the role of decorin in the regulation of stromal fibrillogenesis and corneal transparency in vivo employing a loss-of-function genetic approach using decorin null (dcn-/-) and wild type (dcn+/+) mice and a standard alkali-injury model. A time-dependent ocular examinations with Slit lamp microscope in live animals assessed corneal clarity, haze, and neovascularization levels in normal and injured eyes. Morphometric changes in normal and injured dcn+/+ and dcn-/- corneas, post-euthanasia, were analyzed with Masson's Trichrome and Periodic Acid-Schiff (PAS) histology evaluations. The ultrastructure changes in all corneas were investigated with transmission electron microscopy (TEM). Injury to eye produced clinically relevant corneal haze and neovascularization in dcn-/- and dcn+/+ mice while corneas of uninjured eyes remained clear and avascular. A clinically significant haze and neovascularization appeared in injured dcn-/- corneas compared to the dcn+/+ corneas at day 21 post-injury and not at early tested times. Histological examinations revealed noticeably abnormal morphology and compromised collagen levels in injured dcn-/- corneas compared to the injured/normal dcn+/+ and uninjured dcn-/- corneas. TEM analysis exhibited remarkably uneven collagen fibrils size and distribution in the stroma with asymmetrical organization and loose packing in injured dcn-/- corneas than injured/normal dcn+/+ and uninjured dcn-/- corneas. The minimum and maximum inter-fibril distances were markedly irregular in injured dcn-/- corneas compared to all other corneas. Together, results of clinical, histological, and ultrastructural investigations in a genetic knockout model suggested that decorin influenced stromal fibrillogenesis and transparency in healing cornea.

Authors+Show Affiliations

Harry S. Truman Memorial Veterans' Hospital, Columbia, MO, USA; Departments of Veterinary Medicine & Surgery and Biomedical Sciences, College of Veterinary Medicine, University of Missouri, Columbia, MO, USA.Department of Computer Science, University of Missouri, Columbia, MO, USA.Harry S. Truman Memorial Veterans' Hospital, Columbia, MO, USA; Departments of Veterinary Medicine & Surgery and Biomedical Sciences, College of Veterinary Medicine, University of Missouri, Columbia, MO, USA.Electron Microscopy Core, University of Missouri, Columbia, MO, USA.Harry S. Truman Memorial Veterans' Hospital, Columbia, MO, USA; Departments of Veterinary Medicine & Surgery and Biomedical Sciences, College of Veterinary Medicine, University of Missouri, Columbia, MO, USA.Department of Pathology, Anatomy, and Cell Biology, Translational Cellular Oncology Program, Thomas Jefferson University, Philadelphia, PA, USA.Harry S. Truman Memorial Veterans' Hospital, Columbia, MO, USA; Departments of Veterinary Medicine & Surgery and Biomedical Sciences, College of Veterinary Medicine, University of Missouri, Columbia, MO, USA.Harry S. Truman Memorial Veterans' Hospital, Columbia, MO, USA; Departments of Veterinary Medicine & Surgery and Biomedical Sciences, College of Veterinary Medicine, University of Missouri, Columbia, MO, USA; Mason Eye Institute, School of Medicine, University of Missouri, Columbia, MO, USA. Electronic address: mohanr@health.missouri.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

35031282

Citation

Gupta, Suneel, et al. "Decorin Regulates Collagen Fibrillogenesis During Corneal Wound Healing in Mouse in Vivo." Experimental Eye Research, vol. 216, 2022, p. 108933.
Gupta S, Buyank F, Sinha NR, et al. Decorin regulates collagen fibrillogenesis during corneal wound healing in mouse in vivo. Exp Eye Res. 2022;216:108933.
Gupta, S., Buyank, F., Sinha, N. R., Grant, D. G., Sinha, P. R., Iozzo, R. V., Chaurasia, S. S., & Mohan, R. R. (2022). Decorin regulates collagen fibrillogenesis during corneal wound healing in mouse in vivo. Experimental Eye Research, 216, 108933. https://doi.org/10.1016/j.exer.2022.108933
Gupta S, et al. Decorin Regulates Collagen Fibrillogenesis During Corneal Wound Healing in Mouse in Vivo. Exp Eye Res. 2022;216:108933. PubMed PMID: 35031282.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Decorin regulates collagen fibrillogenesis during corneal wound healing in mouse in vivo. AU - Gupta,Suneel, AU - Buyank,Filiz, AU - Sinha,Nihant R, AU - Grant,DeAna G, AU - Sinha,Prashant R, AU - Iozzo,Renato V, AU - Chaurasia,Shyam S, AU - Mohan,Rajiv R, Y1 - 2022/01/11/ PY - 2021/10/13/received PY - 2021/12/14/revised PY - 2022/01/05/accepted PY - 2023/03/01/pmc-release PY - 2022/1/16/pubmed PY - 2022/3/5/medline PY - 2022/1/15/entrez KW - Collagen fibrillogenesis KW - Cornea KW - Decorin null mice (dcn(−/-)) KW - Transmission electron microscopy (TEM) KW - Wound healing SP - 108933 EP - 108933 JF - Experimental eye research JO - Exp Eye Res VL - 216 N2 - A characteristic rigid spatial arrangement of collagen fibrils in the stroma is critical for corneal transparency. This unique organization of collagen fibrils in corneal stroma can be impacted by the presence and interactions of proteoglycans and extracellular matrix (ECM) proteins in a corneal microenvironment. Earlier studies revealed that decorin, a leucine-rich proteoglycan in stroma, regulates keratocyte-collagen matrix assembly and wound healing in the cornea. This study investigated the role of decorin in the regulation of stromal fibrillogenesis and corneal transparency in vivo employing a loss-of-function genetic approach using decorin null (dcn-/-) and wild type (dcn+/+) mice and a standard alkali-injury model. A time-dependent ocular examinations with Slit lamp microscope in live animals assessed corneal clarity, haze, and neovascularization levels in normal and injured eyes. Morphometric changes in normal and injured dcn+/+ and dcn-/- corneas, post-euthanasia, were analyzed with Masson's Trichrome and Periodic Acid-Schiff (PAS) histology evaluations. The ultrastructure changes in all corneas were investigated with transmission electron microscopy (TEM). Injury to eye produced clinically relevant corneal haze and neovascularization in dcn-/- and dcn+/+ mice while corneas of uninjured eyes remained clear and avascular. A clinically significant haze and neovascularization appeared in injured dcn-/- corneas compared to the dcn+/+ corneas at day 21 post-injury and not at early tested times. Histological examinations revealed noticeably abnormal morphology and compromised collagen levels in injured dcn-/- corneas compared to the injured/normal dcn+/+ and uninjured dcn-/- corneas. TEM analysis exhibited remarkably uneven collagen fibrils size and distribution in the stroma with asymmetrical organization and loose packing in injured dcn-/- corneas than injured/normal dcn+/+ and uninjured dcn-/- corneas. The minimum and maximum inter-fibril distances were markedly irregular in injured dcn-/- corneas compared to all other corneas. Together, results of clinical, histological, and ultrastructural investigations in a genetic knockout model suggested that decorin influenced stromal fibrillogenesis and transparency in healing cornea. SN - 1096-0007 UR - https://www.unboundmedicine.com/medline/citation/35031282/Decorin_regulates_collagen_fibrillogenesis_during_corneal_wound_healing_in_mouse_in_vivo_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-4835(22)00014-8 DB - PRIME DP - Unbound Medicine ER -