Corneal Collagen Cross-Linking With Riboflavin and UVA Regulates Hemangiogenesis and Lymphangiogenesis in Rats

Zhu, Yang; Li, Ling; Reinach, Peter S.; Li, Yun; Ge, Chaoxiang; Qu, Jia; Chen, Wei

doi:10.1167/iovs.17-23036

Cited by 14 publications

(6 citation statements)

References 42 publications

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“…In a recent study by Zhu et al, it was observed that CXL inhibited angiogenesis and lymphangiogenesis for the first 7 days at the corneal vascularization area, but later on, CXL enhanced the effect of angiogenesis and lymphangiogenesis factors. 14 In the same study, it has also been shown that inflammatory cytokines are similarly increased in CXL performed corneas after a temporary suppression period. 14 Similarly, vascularization at the bleb border in our patient might be caused by a combination of CXL-induced proinflammatory cytokines and angiogenic factors.…”

Section: Discussionmentioning

confidence: 80%

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Collagen Crosslinking-assisted Treatment of a Bleb Leak: Enhancement of Vascularization around the Bleb

Bi̇lgi̇han¹,

Aktaş²,

Arıbaş³

et al. 2021

Journal of Current Glaucoma Practice

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A bstract Aim and objective To present a case with bleb leakage treated with collagen crosslinking (CXL). Background Bleb-related complications can cause serious problems even a long time after trabeculectomy. In this case report, we present a relatively unknown treatment method for bleb leakage which might be one of the long-term complications of trabeculectomy. Case description A 60-year-old male patient was admitted to our clinic with a decrease in his left vision. The patient had a history of left trabeculectomy. The bleb leakage was observed. Autologous blood was injected into the bleb area as the first line of treatment. Collagen crosslinking was applied to the bleb area upon the recurrence of the leakage. In the 1st week after the CXL, CXL was repeated in the bleb area upon the observation that the leakage recurred. It was observed that the leakage did not recur and bleb vascularization was triggered after CXL. Conclusion Conjunctival CXL might be a non-invasive, viable method in the management of bleb leakage. It might be applied in conjunction with bandage contact lenses for the treatment of late bleb leaks as an alternative treatment method before going into surgical intervention. Clinical significance As a result of conjunctival CXL application, collagen permeability reduction and neovascularization secondary to CXL application might be effective in preventing bleb leakage. However, further studies are needed to prove this. How to cite this article Aktas Z, Aribas YK, Bilgihan K, et al. Collagen Crosslinking-assisted Treatment of a Bleb Leak: Enhancement of Vascularization around the Bleb. J Curr Glaucoma Pract 2021;15(1):36–39.

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Section: Discussionmentioning

confidence: 80%

“… 14 In the same study, it has also been shown that inflammatory cytokines are similarly increased in CXL performed corneas after a temporary suppression period. 14 Similarly, vascularization at the bleb border in our patient might be caused by a combination of CXL-induced proinflammatory cytokines and angiogenic factors.…”

Section: Discussionmentioning

confidence: 80%

Collagen Crosslinking-assisted Treatment of a Bleb Leak: Enhancement of Vascularization around the Bleb

Bi̇lgi̇han¹,

Aktaş²,

Arıbaş³

et al. 2021

Journal of Current Glaucoma Practice

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“…Zhu et al showed the effectiveness of corneal collagen cross-linking with riboflavin and UVA in reducing damage of acute corneal inflammation. Although the procedure effectively suppresses the hemangiogenesis and lymphangiogenesis in the first week, elevated apoptotic cells, cytokine levels, and neovascularization markers were observed in the second week [52]. Considering the cellular damage caused by UVA light, continued damage during the healing process does not allow rapid recovery in the cornea.…”

Section: Discussionmentioning

confidence: 99%

A unique and biocompatible corneal collagen crosslinking in vivo

Gulzar,

Kaleli,

Köseoğlu

et al. 2024

Preprint

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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 minutes. 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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“… 21 Our previous study also indicates that compacted collagenous architecture possibly obstructs inflammatory cell infiltration. 10 However, the mechanism remains unknown that accounts for how a more compacted ECM impedes immune infiltration.…”

Section: Discussionmentioning

confidence: 99%

“…Neovascularization was evaluated at 3, 7, and 14 days after suture emplacement using a slightly modified method described elsewhere. 10 Briefly, three photographs of each cornea were taken using a digital camera (EOS 5200D; Canon, Tokyo, Japan) under green light at 16 times magnification (10 corneas per group); 360 degree area of corneal new vessels was analyzed at the same magnification using ImageJ software. The area between the innermost new vessel and the limbus was defined as the vascularized area.…”

Section: Methodsmentioning

confidence: 99%

Corneal Collagen Cross-Linking Pretreatment Mitigates Injury-Induced Inflammation, Hemangiogenesis and Lymphangiogenesis In Vivo

Zhu

Reinach

et al. 2021

Trans. Vis. Sci. Tech.

Self Cite

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Purpose The purpose of this study was to evaluate if corneal collagen cross-linking (CXL) pretreatment dampens suture-induced hemangiogenesis and lymphangiogenesis driven by inflammation. Methods Four weeks after CXL pretreatment, suture emplacement was performed in rats. The time dependent effects were compared of this procedure in three groups: (1) suture-induced neovascularization (SNV group); (2) CXL treatment prior to suture-induced neovascularization (CXL + SNV group); (3) Normal control (NC group). Serial morphometric measurements evaluated suture-induced hemangiogenesis and lymphangiogenesis. CD45 and CD68 immunofluorescent staining pattern changes determined immune cell activation, stromal leucocyte, and macrophage infiltration. The real-time quantitative polymerase chain reaction (RT-qPCR) determined angiogenic and lymphangiogenic gene expression level changes. Western blots evaluated protein expression levels of vascular endothelial cell CD31 and lymphatic vessel endothelial hyaluronan receptor (LYVE-1). Results On days 7 and 14 after suture emplacement, the rises in angiogenesis, lymphangiogenesis, CD45+ and CD68+ cell infiltration were less in the CXL pretreated (CXL + SNV) group than in the untreated (SNV) group. Angiogenic and lymphangiogenic mRNA levels and CD31 and LYVE-1 protein and proinflammatory cytokines were also suppressed, confirming that CXL pretreatment improved the wound healing response. Conclusions CXL pretreatment inhibits injury-induced angiogenesis and lymphangiogenesis. These reductions suggest that prior CXL therapy decrease ocular inflammation reactivated by secondary trauma. Translational Relevance CXL pretreatment induces increases in stromal stiffness which in turn reduces trauma or microbial driven increases in inflammation, angiogenesis, and lymphangiogenesis. These beneficial effects suggest that this novel procedure may improve therapeutic management of trauma-induced corneal disease in a clinical setting.

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Corneal Collagen Cross-Linking With Riboflavin and UVA Regulates Hemangiogenesis and Lymphangiogenesis in Rats

Cited by 14 publications

References 42 publications

Collagen Crosslinking-assisted Treatment of a Bleb Leak: Enhancement of Vascularization around the Bleb

Collagen Crosslinking-assisted Treatment of a Bleb Leak: Enhancement of Vascularization around the Bleb

A unique and biocompatible corneal collagen crosslinking in vivo

Corneal Collagen Cross-Linking Pretreatment Mitigates Injury-Induced Inflammation, Hemangiogenesis and Lymphangiogenesis In Vivo

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