Effects of Regorafenib, a Multi-Kinase Inhibitor, on Conjunctival Scarring in a Canine Filtration Surgery Model in Comparison with Mitomycin-C

Nemoto, Emika; Kojima, Shota; Sugiyama, Tetsuya; Jin, Denan; Maeda, Michiaki; Kohmoto, Ryohsuke; Ueki, Mari; Oku, Hidehiro; Ikeda, Tsunehiko

doi:10.3390/ijms21010063

Cited by 4 publications

(3 citation statements)

References 37 publications

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“…Previous clinical trials have demonstrated the efficacy of one particular medication from the aforementioned list in treating open angle glaucoma or ocular hypertension ( Brigell et al, 2022 ). In animal studies, three medications have exhibited anti-fibrotic properties and neuroprotective effects ( Nemoto et al, 2019 ; Zhang et al, 2019 ; Kim et al, 2021 ). Additionally, two medications have been found to interfere with the TGF-β/p38 signaling pathway, modify cellular structure, and reduce extracellular matrix (ECM) at the cellular level ( Luo et al, 2014 ; Song et al, 2022 ) ( Supplementary Table S3 ).…”

Section: Resultsmentioning

confidence: 99%

Identification of immune-related biomarkers for glaucoma using gene expression profiling

Wang,

Pu,

Tan

et al. 2024

Front. Genet.

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Introduction: Glaucoma, a principal cause of irreversible vision loss, is characterized by intricate optic neuropathy involving significant immune mechanisms. This study seeks to elucidate the molecular and immune complexities of glaucoma, aiming to improve our understanding of its pathogenesis.Methods: Gene expression profiles from glaucoma patients were analyzed to identify immune-related differentially expressed genes (DEGs). Techniques used were weighted gene co-expression network analysis (WGCNA) for network building, machine learning algorithms for biomarker identification, establishment of subclusters related to immune reactions, and single-sample gene set enrichment analysis (ssGSEA) to explore hub genes’ relationships with immune cell infiltration and immune pathway activation. Validation was performed using an NMDA-induced excitotoxicity model and RT-qPCR for hub gene expression measurement.Results: The study identified 409 DEGs differentiating healthy individuals from glaucoma patients, highlighting the immune response’s significance in disease progression. Immune cell infiltration analysis revealed elevated levels of activated dendritic cells, natural killer cells, monocytes, and immature dendritic cells in glaucoma samples. Three hub genes, CD40LG, TEK, and MDK, were validated as potential diagnostic biomarkers for high-risk glaucoma patients, showing increased expression in the NMDA-induced excitotoxicity model.Discussion: The findings propose the three identified immune-related genes (IRGs) as novel diagnostic markers for glaucoma, offering new insights into the disease's pathogenesis and potential therapeutic targets. The strong correlation between these IRGs and immune responses underscores the intricate role of immunity in glaucoma, suggesting a shift in the approach to its diagnosis and treatment.

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Section: Resultsmentioning

confidence: 99%

Identification of immune-related biomarkers for glaucoma using gene expression profiling

Wang,

Pu,

Tan

et al. 2024

Front. Genet.

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“…To explain this phenomenon, unlike tube shunt surgery, which produces delayed drainage of AH to the equatorial region of the eye due to the distance between the location of filtration and the conjunctival incision, trabeculectomy causes an immediate filtration of AH near the conjunctival incision that increases the risk of leakage. In addition, the application of antimetabolites such as mitomycin C (MMC) and 5-fluorouracil (5-FU) in trabeculectomy is considered to be related since they are thought to be the cause of an increased probability of bleb leakage 78. Histological studies of MMC blebs have shown an irregular surface epithelium and a largely avascular and acellular subepithelium of loosely arranged connective tissue, which may explain the delayed bleb leaks seen frequently after MMC-augmented glaucoma surgery 79.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, the application of antimetabolites such as mitomycin C (MMC) and 5-fluorouracil (5-FU) in trabeculectomy is considered to be related since they are thought to be the cause of an increased probability of bleb leakage. 78 Histological studies of MMC blebs have shown an irregular surface epithelium and a largely avascular and acellular subepithelium of loosely arranged connective tissue, which may explain the delayed bleb Open access leaks frequently after MMC-augmented glaucoma surgery. 79 The association between delayed bleb leaks and thin-walled, avascular blebs has been previously reported, with these leaks being more frequent after full-thickness procedures.…”

Section: Open Accessmentioning

confidence: 99%

Comparison of tube shunt implantation and trabeculectomy for glaucoma: a systematic review and meta-analysis

et al. 2023

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ObjectiveTo compare the efficacy and safety of tube shunt implantation with trabeculectomy in the treatment of patients with glaucoma.MethodsA systematic literature search was performed for studies comparing tube with trabeculectomy in patients with glaucoma (final search date: 27 February 2022). Comparisons between tube and trabeculectomy were grouped by the type of tube (Ahmed, Baerveldt, Ex-PRESS and XEN). The primary endpoints included intraocular pressure (IOP), IOP reduction (IOPR), IOPR percentage (IOPR%), complete success rate (CSR), qualified success rate (QSR) and adverse events (AEs).ResultsForty-nine studies were included in this meta-analysis and presented data for 3795 eyes (Ahmed: 670, Baerveldt: 561, Ex-PRESS: 473, XEN: 199, trabeculectomy: 1892). Ahmed and Ex-PRESS were similar to trabeculectomy in terms of IOP outcomes and success rate (Ahmed vs trabeculectomy: IOPR%: mean difference (MD)=1.34 (–5.35, 8.02), p=0.69; Ex-PRESS vs trabeculectomy: IOPR%: MD=0.12 (–3.07, 3.31), p=0.94). The IOP outcomes for Baerveldt were worse than those for trabeculectomy (IOPR%: MD=−7.51 (–10.68, –4.35), p<0.00001), but the QSR was higher. No significant difference was shown for the CSR. XEN was worse than trabeculectomy in terms of IOP outcomes (IOPR%: MD=−7.87 (–13.55, –2.18), p=0.007), while the success rate was similar. Ahmed and Ex-PRESS had a lower incidence of AEs than trabeculectomy. Baerveldt had a lower incidence of bleb leakage/wound leakage, hyphaema and hypotonic maculopathy than trabeculectomy but a higher incidence of concurrent cataracts, diplopia/strabismus and tube erosion. The incidence of AEs was similar for the XEN and trabeculectomy procedures.ConclusionCompared with trabeculectomy, both Ahmed and Ex-PRESS appear to be associated with similar ocular hypotensive effects and lower incidences of AEs. However, Baerveldt and XEN cannot achieve sufficient reductions in IOP outcomes similar to those of trabeculectomy.PROSPERO registration numberCRD42021257852.

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Osteoporosis in children and adolescents: when to suspect and how to diagnose it

et al. 2022

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Early recognition of osteoporosis in children and adolescents is important in order to establish an appropriate diagnosis of the underlying condition and to initiate treatment if necessary. In this review, we present the diagnostic work-up, and its pitfalls, of pediatric patients suspected of osteoporosis including a careful collection of the medical and personal history, a complete physical examination, biochemical data, molecular genetics, and imaging techniques. The most recent and relevant literature has been reviewed to offer a broad overview on the topic. Genetic and acquired pediatric bone disorders are relatively common and cause substantial morbidity. In recent years, there has been significant progress in the understanding of the genetic and molecular mechanistic basis of bone fragility and in the identification of acquired causes of osteoporosis in children. Specifically, drugs that can negatively impact bone health (e.g. steroids) and immobilization related to acute and chronic diseases (e.g. Duchenne muscular dystrophy) represent major risk factors for the development of secondary osteoporosis and therefore an indication to screen for bone mineral density and vertebral fractures. Long-term studies in children chronically treated with steroids have resulted in the development of systematic approaches to diagnose and manage pediatric osteoporosis.Conclusions: Osteoporosis in children requires consultation with and/or referral to a pediatric bone specialist. This is particularly relevant since children possess the unique ability for spontaneous and medication-assisted recovery, including reshaping of vertebral fractures. As such, pediatricians have an opportunity to improve bone mass accrual and musculoskeletal health in osteoporotic children. What is Known:• Both genetic and acquired pediatric disorders can compromise bone health and predispose to fractures early in life.• The identification of children at risk of osteoporosis is essential to make a timely diagnosis and start the treatment, if necessary. What is New:• Pediatricians have an opportunity to improve bone mass accrual and musculoskeletal health in osteoporotic children and children at risk of osteoporosis.• We offer an extensive but concise overview about the risk factors for osteoporosis and the diagnostic work-up (and its pitfalls) of pediatric patients suspected of osteoporosis.

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Effects of Regorafenib, a Multi-Kinase Inhibitor, on Conjunctival Scarring in a Canine Filtration Surgery Model in Comparison with Mitomycin-C

Cited by 4 publications

References 37 publications

Identification of immune-related biomarkers for glaucoma using gene expression profiling

Identification of immune-related biomarkers for glaucoma using gene expression profiling

Comparison of tube shunt implantation and trabeculectomy for glaucoma: a systematic review and meta-analysis

Osteoporosis in children and adolescents: when to suspect and how to diagnose it

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