A unique and biocompatible corneal collagen crosslinking in vivo

Abstract Corneal crosslinking (CXL) is a widely applied technique to halt the progression of ectatic diseases through increasing the thickness and mechanical stiffness of the cornea. This study investigated the biocompatibility and efficiency of a novel CXL procedure using ruthenium and blue light i...

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Main Authors: Ayesha Gulzar, Humeyra N Kaleli, Gülsüm D Köseoğlu, Murat Hasanreisoğlu, Ayşe Yıldız, Afsun Şahin, Seda Kizilel
Format: Article
Language:English
Published: Nature Portfolio 2024-10-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-024-71871-9
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author Ayesha Gulzar
Humeyra N Kaleli
Gülsüm D Köseoğlu
Murat Hasanreisoğlu
Ayşe Yıldız
Afsun Şahin
Seda Kizilel
author_facet Ayesha Gulzar
Humeyra N Kaleli
Gülsüm D Köseoğlu
Murat Hasanreisoğlu
Ayşe Yıldız
Afsun Şahin
Seda Kizilel
author_sort Ayesha Gulzar
collection DOAJ
description Abstract Corneal crosslinking (CXL) is a widely applied technique to halt the progression of ectatic diseases through increasing the thickness and mechanical stiffness of the cornea. This study investigated the biocompatibility and efficiency of a novel CXL procedure using ruthenium and blue light in rat corneas and evaluated parameters important for clinical application. To perform the CXL procedure, the corneal epithelium of rats was removed under anaesthesia, followed by the application of a solution containing ruthenium and sodium persulfate (SPS). The corneas were then exposed to blue light at 430 nm at 3 mW/cm2 for 5 min. Rat corneas were examined and evaluated for corneal opacity, corneal and limbal neovascularization, and corneal epithelial regeneration on days 0, 1, 3, 6, 8, and 14. On day 28, the corneas were isolated for subsequent tissue follow-up and analysis. CXL with ruthenium and blue light showed rapid epithelial healing, with 100% regeneration of the corneal epithelium and no corneal opacity on day 6. The ruthenium group also exhibited significantly reduced corneal (p < 0.01) and limbal neovascularization (p < 0.001). Histological analysis revealed no signs of cellular damage or apoptosis, which further confirms the biocompatibility and nontoxicity of our method. Confocal and scanning electron microscopy (SEM) images confirmed high density of collagen fibrils, indicating efficient crosslinking and enhanced structural integrity. This study is unique that demonstrates in vivo safety, biocompatibility, and functionality of ruthenium and blue light CXL. This approach can prevent toxicity caused by UV-A light and can be an immediate alternative compared to the existing crosslinking procedures that have side effects and clinical risks for the patients.
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spelling doaj-art-4b521b97fcb548859fb40ac1da68dd3b2025-08-20T03:16:47ZengNature PortfolioScientific Reports2045-23222024-10-0114111310.1038/s41598-024-71871-9A unique and biocompatible corneal collagen crosslinking in vivoAyesha Gulzar0Humeyra N Kaleli1Gülsüm D Köseoğlu2Murat Hasanreisoğlu3Ayşe Yıldız4Afsun Şahin5Seda Kizilel6Biomedical Sciences and Engineering, Koç UniversityKoç University Research Center for Translational Medicine (KUTTAM), Koç UniversityKoç University Research Center for Translational Medicine (KUTTAM), Koç UniversityKoç University Research Center for Translational Medicine (KUTTAM), Koç UniversityDepartment of Ophthalmology, Koç University School of MedicineKoç University Research Center for Translational Medicine (KUTTAM), Koç UniversityBiomedical Sciences and Engineering, Koç UniversityAbstract Corneal crosslinking (CXL) is a widely applied technique to halt the progression of ectatic diseases through increasing the thickness and mechanical stiffness of the cornea. This study investigated the biocompatibility and efficiency of a novel CXL procedure using ruthenium and blue light in rat corneas and evaluated parameters important for clinical application. To perform the CXL procedure, the corneal epithelium of rats was removed under anaesthesia, followed by the application of a solution containing ruthenium and sodium persulfate (SPS). The corneas were then exposed to blue light at 430 nm at 3 mW/cm2 for 5 min. Rat corneas were examined and evaluated for corneal opacity, corneal and limbal neovascularization, and corneal epithelial regeneration on days 0, 1, 3, 6, 8, and 14. On day 28, the corneas were isolated for subsequent tissue follow-up and analysis. CXL with ruthenium and blue light showed rapid epithelial healing, with 100% regeneration of the corneal epithelium and no corneal opacity on day 6. The ruthenium group also exhibited significantly reduced corneal (p < 0.01) and limbal neovascularization (p < 0.001). Histological analysis revealed no signs of cellular damage or apoptosis, which further confirms the biocompatibility and nontoxicity of our method. Confocal and scanning electron microscopy (SEM) images confirmed high density of collagen fibrils, indicating efficient crosslinking and enhanced structural integrity. This study is unique that demonstrates in vivo safety, biocompatibility, and functionality of ruthenium and blue light CXL. This approach can prevent toxicity caused by UV-A light and can be an immediate alternative compared to the existing crosslinking procedures that have side effects and clinical risks for the patients.https://doi.org/10.1038/s41598-024-71871-9CorneaCollagenCrosslinkingIn vivoRutheniumBlue light
spellingShingle Ayesha Gulzar
Humeyra N Kaleli
Gülsüm D Köseoğlu
Murat Hasanreisoğlu
Ayşe Yıldız
Afsun Şahin
Seda Kizilel
A unique and biocompatible corneal collagen crosslinking in vivo
Scientific Reports
Cornea
Collagen
Crosslinking
In vivo
Ruthenium
Blue light
title A unique and biocompatible corneal collagen crosslinking in vivo
title_full A unique and biocompatible corneal collagen crosslinking in vivo
title_fullStr A unique and biocompatible corneal collagen crosslinking in vivo
title_full_unstemmed A unique and biocompatible corneal collagen crosslinking in vivo
title_short A unique and biocompatible corneal collagen crosslinking in vivo
title_sort unique and biocompatible corneal collagen crosslinking in vivo
topic Cornea
Collagen
Crosslinking
In vivo
Ruthenium
Blue light
url https://doi.org/10.1038/s41598-024-71871-9
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