The research progress on the molecular mechanism of corneal cross-linking in keratoconus treatment

Yang, Qingyu; Wang, Shurong; He, Yuxi; Zhang, Yan

doi:10.1016/j.clae.2022.101795

Cited by 8 publications

(8 citation statements)

References 65 publications

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“…Long-term changes in NGF levels after CXL were also not detected. Bence Lajos Kolozsvári’s findings were similar [ 23 , 35 ].…”

Section: Discussionmentioning

confidence: 61%

Level of Secretion and the Role of the Nerve Growth Factor in Patients with Keratoconus before and after Collagen Fibre Cross-Linking Surgery

Krok,

Wróblewska-Czajka,

Łach-Wojnarowicz

et al. 2023

IJMS

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Background: The aim of this study was to analyse the concentration of the nerve growth factor (NGF-β) in patients with keratoconus (KC) who are undergoing collagen fibre cross-linking (CXL) surgery in order to better understand the pathogenesis of this disease and observe the molecular changes occurring after the procedure. Among many cytokines, β-NGF seems to play an important role in the healing processes of corneal damage. Therefore, its role in the regenerative process after CXL treatment may affect the course of treatment and its final results. Tear samples from 52 patients were collected in this prospective study. Additionally, the patients also had a number of tests performed, including corneal topography using optical coherence tomography. Flat (K 1), steep (K 2), cylindrical (CYL), and central corneal thickness (CCT) keratometry were assessed. The tear samples were collected, and other tests were performed before the CXL procedure and afterwards, during the 12-month follow-up period. The NGF concentration was measured using the Bio-Plex Magnetic Luminex Assay. Lower levels of NGF-β were detected in the KC patients than in the control group (p < 0.001). The day after the procedure, the NGF-β level was significantly lower (on average by 2.3 pg/mL) (p = 0.037) than before the procedure, after which, the level of the reagent increases, but only in the group with the advanced cone, one month after CXL it was significantly higher (p = 0.047). Regarding the correlation of NGF with topographic measurements, the following were found: NGF-β correlates significantly (p < 0.05) and positively (r > 0) with K1 before the CXL procedure; NGF-β correlates significantly (p < 0.05) and positively (r > 0) with K1 one month after CXL; NGF-β correlates significantly (p < 0.05) and positively (r > 0) with CYL nine months after CXL; and, after twelve months, NGF-β correlates significantly (p < 0.05) and positively (r > 0) with K2 and K1. Corneal sensitivity did not statistically and significantly correlate with the level of NGF-β secretion. Our study suggests that NGF may be crucial in the development and progression of KC as well as in the repair mechanisms after CXL surgery. Further research is needed on the role of NGF and other inflammatory biomarkers for rapid diagnosis and selection of targeted therapy in patients with keratoconus.

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“…Long-term changes in NGF levels after CXL were also not detected. Bence Lajos Kolozsvári’s findings were similar [ 23 , 35 ].…”

Section: Discussionmentioning

confidence: 61%

Level of Secretion and the Role of the Nerve Growth Factor in Patients with Keratoconus before and after Collagen Fibre Cross-Linking Surgery

Krok,

Wróblewska-Czajka,

Łach-Wojnarowicz

et al. 2023

IJMS

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“…Corneal cross-linking(CXL) can effectively halt the progression of KC by strengthen collagen fibril linkages and therefore the biomechanical properties of cornea. LOX and MMP9 are two enzymes that regulate the formation and maturation of collagen [ 61 ]. Decrease in activity and quantity of LOX in KC patients resulted in cross-linking disorder and weakened biomechanical properties of the cornea [ 62 ].…”

Section: Discussionmentioning

confidence: 99%

The candidate proteins associated with keratoconus: A meta-analysis and bioinformatic analysis

Song,

et al. 2024

PLoS ONE

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Purpose Keratoconus (KC) is a multifactorial disorder. This study aimed to conduct a systematic meta-analysis to exclusively explore the candidate proteins associated with KC pathogenesis. Methods Relevant literature published in the last ten years in Pubmed, Web of Science, Cochrane, and Embase databases were searched. Protein expression data were presented as the standard mean difference (SMD) and 95% confidence intervals (CI). The meta-analysis is registered on PROSPERO, registration number CRD42022332442 and was conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement (PRISMA). GO and KEGG enrichment analysis were performed, as well as the miRNAs and chemicals targeting the candidate proteins were predicted. PPI was analyzed to screen the hub proteins, and their expression was verified by RT-qPCR. Results A total of 21 studies were included in the meta-analysis, involving 346 normal eyes and 493 KC eyes. 18 deregulated proteins with significant SMD values were subjected to further analysis. In which, 7 proteins were up-regulated in KC compared with normal controls, including IL6 (SMD 1.54, 95%CI [0.85, 2.24]), IL1B (SMD 2.07, 95%CI [0.98, 3.16]), TNF (SMD 2.1, 95%CI [0.24, 3.96]), and MMP9 (SMD 1.96, 95%CI [0.68, 3.24]). While 11 proteins were down-regulated in KC including LOX (SMD 2.54, 95%CI [-4.51, -0.57]). GO and KEGG analysis showed that the deregulated proteins were involved in inflammation, extracellular matrix (ECM) remodeling, and apoptosis. MMP9, IL6, LOX, TNF, and IL1B were regarded as hub proteins according to the PPI analysis, and their transcription changes in stromal fibroblasts of KC were consistent with the results of the meta-analysis. Moreover, 10 miRNAs and two natural polyphenols interacting with hub proteins were identified. Conclusion This study obtained 18 candidate proteins and demonstrated altered cytokine profiles, ECM remodeling, and apoptosis in KC patients through meta-analysis and bioinformatic analysis. It will provide biomarkers for further understanding of KC pathogenesis, and potential therapeutic targets for the drug treatment of KC.

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“…The appropriate balance of growth factors, cytokines, proteases and extracellular matrix (ECM) signaling maintains or restores corneal integrity [6]. Inflammatory mediators and immune cells contribute to ECM modeling by modulating cellular signaling pathways that regulate ECM component production, such as collagens, proteoglycans, cross-linking enzymes, and proteolysis enzymes [7].…”

Section: Inflammatory Factors and Immune Components In Ocular Surface...mentioning

confidence: 99%

Ocular surface inflammation and ectatic corneal disorders

Erdinest

Wajnsztajn

London

et al. 2023

Current Opinion in Allergy &Amp; Clinical Immunology

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Purpose of review Inflammatory mediators are a focus of recent corneal ectasia (CE) research and are a profound, modifiable contributor to CE in general and keratoconus (KC) in particular, opening a path to explore new methods of control. As advanced imaging technology and expanded population screening allow for earlier detection, the possibility of early intervention can profoundly change the prognosis of CE. Recent findings Significant increases in the inflammatory mediators and immune components have been observed in the cornea, tear fluid, and blood of ectasia patients, while inflammation dampeners such as vitamin D and their receptors are reduced. Atopy and allergy have a strong association with KC, known to increase itch factors and stimulate eye rubbing, a risk factor in ectasia pathogenesis. Management of atopy or allergic conditions and topical anti-inflammatories has helped stabilize CE disease. Summary Strategies such as monitoring inflammatory factors and using immune or inflammatory modulators, including managing subclinical inflammation, may be clinically beneficial in stabilizing the disease and improving outcomes. The detected factors are biomarkers, but as yet unproven to be sensitive or specific enough to be considered biomarkers for early detection of CE. The establishment of such biomarkers could improve the therapeutic outcome.

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The research progress on the molecular mechanism of corneal cross-linking in keratoconus treatment

Cited by 8 publications

References 65 publications

Level of Secretion and the Role of the Nerve Growth Factor in Patients with Keratoconus before and after Collagen Fibre Cross-Linking Surgery

Level of Secretion and the Role of the Nerve Growth Factor in Patients with Keratoconus before and after Collagen Fibre Cross-Linking Surgery

The candidate proteins associated with keratoconus: A meta-analysis and bioinformatic analysis

Ocular surface inflammation and ectatic corneal disorders

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