Corneal Wound Healing in the Presence of Antifibrotic Antibody Targeting Collagen Fibrillogenesis: A Pilot Study
Highly organized collagen fibrils interlacing with proteoglycans form the crucial architecture of the cornea and facilitate its transparency. Corneal scarring from accidental injury, surgery, or infection alters this highly organized tissue, causing severe consequences, including blindness. There ar...
Main Authors: | , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2023-08-01
|
Series: | International Journal of Molecular Sciences |
Subjects: | |
Online Access: | https://www.mdpi.com/1422-0067/24/17/13438 |
_version_ | 1797582371684352000 |
---|---|
author | Zeba A. Syed Tatyana Milman Jolanta Fertala Andrzej Steplewski Andrzej Fertala |
author_facet | Zeba A. Syed Tatyana Milman Jolanta Fertala Andrzej Steplewski Andrzej Fertala |
author_sort | Zeba A. Syed |
collection | DOAJ |
description | Highly organized collagen fibrils interlacing with proteoglycans form the crucial architecture of the cornea and facilitate its transparency. Corneal scarring from accidental injury, surgery, or infection alters this highly organized tissue, causing severe consequences, including blindness. There are no pharmacological or surgical methods to effectively and safely treat excessive corneal scarring. Thus, we tested the anticorneal scarring utility of a rationally designed anticollagen antibody (ACA) whose antifibrotic effects have already been demonstrated in nonocular models. Utilizing a rabbit model with an incisional corneal wound, we analyzed ACA’s effects on forming collagen and proteoglycan-rich extracellular matrices in scar neotissue. We used microscopic and spectroscopic techniques to quantify these components and measure crucial parameters characterizing the structure and organization of collagen fibrils. Moreover, we analyzed the spatial distribution of collagen and proteoglycans in normal and healing corneas. Our study demonstrated significant changes in the quality and quantity of the analyzed molecules synthesized in scar neotissue. It showed that these changes extend beyond incision margins. It also showed ACA’s positive impact on some crucial parameters defining proper cornea structure. This pilot study provides a stepping stone for future tests of therapeutic approaches that target corneal extracellular scar matrix assembly. |
first_indexed | 2024-03-10T23:21:11Z |
format | Article |
id | doaj.art-248bc916d3ff448a87cdfa941119d5cc |
institution | Directory Open Access Journal |
issn | 1661-6596 1422-0067 |
language | English |
last_indexed | 2024-03-10T23:21:11Z |
publishDate | 2023-08-01 |
publisher | MDPI AG |
record_format | Article |
series | International Journal of Molecular Sciences |
spelling | doaj.art-248bc916d3ff448a87cdfa941119d5cc2023-11-19T08:17:15ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-08-0124171343810.3390/ijms241713438Corneal Wound Healing in the Presence of Antifibrotic Antibody Targeting Collagen Fibrillogenesis: A Pilot StudyZeba A. Syed0Tatyana Milman1Jolanta Fertala2Andrzej Steplewski3Andrzej Fertala4Wills Eye Hospital, Philadelphia, PA 19107, USAWills Eye Hospital, Philadelphia, PA 19107, USADepartment of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Curtis Building, Room 501, 1015 Walnut Street, Philadelphia, PA 19107, USADepartment of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Curtis Building, Room 501, 1015 Walnut Street, Philadelphia, PA 19107, USADepartment of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Curtis Building, Room 501, 1015 Walnut Street, Philadelphia, PA 19107, USAHighly organized collagen fibrils interlacing with proteoglycans form the crucial architecture of the cornea and facilitate its transparency. Corneal scarring from accidental injury, surgery, or infection alters this highly organized tissue, causing severe consequences, including blindness. There are no pharmacological or surgical methods to effectively and safely treat excessive corneal scarring. Thus, we tested the anticorneal scarring utility of a rationally designed anticollagen antibody (ACA) whose antifibrotic effects have already been demonstrated in nonocular models. Utilizing a rabbit model with an incisional corneal wound, we analyzed ACA’s effects on forming collagen and proteoglycan-rich extracellular matrices in scar neotissue. We used microscopic and spectroscopic techniques to quantify these components and measure crucial parameters characterizing the structure and organization of collagen fibrils. Moreover, we analyzed the spatial distribution of collagen and proteoglycans in normal and healing corneas. Our study demonstrated significant changes in the quality and quantity of the analyzed molecules synthesized in scar neotissue. It showed that these changes extend beyond incision margins. It also showed ACA’s positive impact on some crucial parameters defining proper cornea structure. This pilot study provides a stepping stone for future tests of therapeutic approaches that target corneal extracellular scar matrix assembly.https://www.mdpi.com/1422-0067/24/17/13438corneascarringcollagenproteoglycanstherapeutic antibodyantifibrotic |
spellingShingle | Zeba A. Syed Tatyana Milman Jolanta Fertala Andrzej Steplewski Andrzej Fertala Corneal Wound Healing in the Presence of Antifibrotic Antibody Targeting Collagen Fibrillogenesis: A Pilot Study International Journal of Molecular Sciences cornea scarring collagen proteoglycans therapeutic antibody antifibrotic |
title | Corneal Wound Healing in the Presence of Antifibrotic Antibody Targeting Collagen Fibrillogenesis: A Pilot Study |
title_full | Corneal Wound Healing in the Presence of Antifibrotic Antibody Targeting Collagen Fibrillogenesis: A Pilot Study |
title_fullStr | Corneal Wound Healing in the Presence of Antifibrotic Antibody Targeting Collagen Fibrillogenesis: A Pilot Study |
title_full_unstemmed | Corneal Wound Healing in the Presence of Antifibrotic Antibody Targeting Collagen Fibrillogenesis: A Pilot Study |
title_short | Corneal Wound Healing in the Presence of Antifibrotic Antibody Targeting Collagen Fibrillogenesis: A Pilot Study |
title_sort | corneal wound healing in the presence of antifibrotic antibody targeting collagen fibrillogenesis a pilot study |
topic | cornea scarring collagen proteoglycans therapeutic antibody antifibrotic |
url | https://www.mdpi.com/1422-0067/24/17/13438 |
work_keys_str_mv | AT zebaasyed cornealwoundhealinginthepresenceofantifibroticantibodytargetingcollagenfibrillogenesisapilotstudy AT tatyanamilman cornealwoundhealinginthepresenceofantifibroticantibodytargetingcollagenfibrillogenesisapilotstudy AT jolantafertala cornealwoundhealinginthepresenceofantifibroticantibodytargetingcollagenfibrillogenesisapilotstudy AT andrzejsteplewski cornealwoundhealinginthepresenceofantifibroticantibodytargetingcollagenfibrillogenesisapilotstudy AT andrzejfertala cornealwoundhealinginthepresenceofantifibroticantibodytargetingcollagenfibrillogenesisapilotstudy |