Activated Blood Coagulation Factor X (FXa) Contributes to the Development of Traumatic PVR Through Promoting RPE Epithelial-Mesenchymal Transition

Han, Han; Zhao, Xiao Hui; Liao, Mengyu; Song, Yinting; You, Caiyun; Dong, Xue; Yang, Xueli; Wang, Xiaohong; Huang, Bo; Du, Mei; Yan, Hua

doi:10.1167/iovs.62.9.29

Cited by 7 publications

(10 citation statements)

References 38 publications

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“…Other growth factors and cytokines such as epidermal growth factor (EGF), TNF-α, interleukin 6 (IL-6), fibroblast growth factor 2 (FGF2), Gremlin or Factor Xa have also been used to induce EMT and study EMT markers, proliferation, migration, and morphology of RPE cells [29,30,37,38]. These models could provide alternatives to the TGF-β-induced EMT model but remain to be more extensively studied.…”

Section: Emt Induction By Growth Factors or Cytokinesmentioning

confidence: 99%

“…Indeed, the proliferative and inflammatory vitreous reaction following the injection of cells, cytokines, growth factors and/or other blood components reproduce different stages of PVR [73,115,116]. In addition, surgical techniques mimicking ocular trauma reproduce the most frequent cause of PVR, disrupting the blood-retinal barrier (BRB), and allowing the subsequent activation and recruitment of macrophages, fibroblasts, and glial cells [37,117]. Interestingly, PVR has also been induced by associating ocular trauma with intravitreal injections or the simultaneous injection of different cell types and/or active compounds [52,70,117,118].…”

Section: Rabbit Pvr Modelsmentioning

confidence: 99%

“…The first described injection model reproducing PVR in rabbits was described in 1984, based on the induction of a "fibroplasia" by injecting dermal connective tissue into the vitreous [119]. Since then, the intravitreal injection of cells or other compounds has been widely used in rabbit PVR models [37,59,61,70].…”

Section: Rabbit Pvr Modelsmentioning

confidence: 99%

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Experimental Models to Study Epithelial-Mesenchymal Transition in Proliferative Vitreoretinopathy

Datlibagi

Zein-El-Din

Frohly

et al. 2023

IJMS

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Proliferative vitreoretinal diseases (PVDs) encompass proliferative vitreoretinopathy (PVR), epiretinal membranes, and proliferative diabetic retinopathy. These vision-threatening diseases are characterized by the development of proliferative membranes above, within and/or below the retina following epithelial-mesenchymal transition (EMT) of the retinal pigment epithelium (RPE) and/or endothelial-mesenchymal transition of endothelial cells. As surgical peeling of PVD membranes remains the sole therapeutic option for patients, development of in vitro and in vivo models has become essential to better understand PVD pathogenesis and identify potential therapeutic targets. The in vitro models range from immortalized cell lines to human pluripotent stem-cell-derived RPE and primary cells subjected to various treatments to induce EMT and mimic PVD. In vivo PVR animal models using rabbit, mouse, rat, and swine have mainly been obtained through surgical means to mimic ocular trauma and retinal detachment, and through intravitreal injection of cells or enzymes to induce EMT and investigate cell proliferation and invasion. This review offers a comprehensive overview of the usefulness, advantages, and limitations of the current models available to investigate EMT in PVD.

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Section: Emt Induction By Growth Factors or Cytokinesmentioning

confidence: 99%

Section: Rabbit Pvr Modelsmentioning

confidence: 99%

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Experimental Models to Study Epithelial-Mesenchymal Transition in Proliferative Vitreoretinopathy

Datlibagi

Zein-El-Din

Frohly

et al. 2023

IJMS

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“…The early fibrotic appearance of cell is an important part in pathological process of PVR [2] . Some studies have showed that abnormal activation of retinal pigment epithelium (RPE) cells play significant roles in the development of fibrosis during of PVR [3][4][5] . The conversion of RPE cells into fibroblast-like cells accelerates the development of PVR [6] .…”

Section: Introductionmentioning

confidence: 99%

Inhibition of EGFR attenuates EGF-induced activation of retinal pigment epithelium cell via EGFR/AKT signaling pathway

Zhu,

Zhang,

Wang

et al. 2024

Int J Ophthalmol

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AIM: To explore the effect of epidermal growth factor receptor (EGFR) inhibition by erlotinib and EGFR siRNA on epidermal growth factor (EGF)-induced activation of retinal pigment epithelium (RPE) cells. METHODS: Human RPE cell line (ARPE-19 cells) was activated by 100 ng/mL EGF. Erlotinib and EGFR siRNA were used to intervene EGF treatment. Cellular viability, proliferation, and migration were detected by methyl thiazolyl tetrazolium (MTT) assay, bromodeoxyuridine (BrdU) staining assay and wound healing assay, respectively. EGFR/protein kinase B (AKT) pathway proteins and N-cadherin, α-smooth muscle actin (α-SMA), and vimentin were tested by Western blot assay. EGFR was also determined by immunofluorescence staining. RESULTS: EGF treatment for 24h induced a significant increase of ARPE-19 cells’ viability, proliferation and migration, phosphorylation of EGFR/AKT proteins, and decreased total EGFR expression. Erlotinib suppressed ARPE-19 cells’ viability, proliferation and migration through down regulating total EGFR and AKT protein expressions. Erlotinib also inhibited EGF-induced an increase of proliferative and migrative ability in ARPE-19 cells and clearly suppressed EGF-induced EGFR/AKT proteins phosphorylation and decreased expression of N-cadherin, α-SMA, and vimentin proteins. Similarly, EGFR inhibition by EGFR siRNA significantly affected EGF-induced an increase of cell proliferation, viability, and migration, phosphorylation of EGFR/AKT proteins, and up-regulation of N-cadherin, α-SMA, and vimentin proteins. CONCLUSION: Erlotinib and EGFR-knockdown suppress EGF-induced cell viability, proliferation, and migration via EGFR/AKT pathway in RPE cells. EGFR inhibition may be a possible therapeutic approach for proliferative vitreoretinopathy (PVR).

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“…Recently, advances in research and data analytics have promoted our understanding and management of ocular trauma. Molecular biology of human tissues and animal models have revealed inflammation with unique molecular pathways in the pathogenesis of various types of ocular trauma ( 2 ). The application of in vivo imaging techniques, such as optical coherence tomography ( 3 ) and adaptive optics laser scanning ophthalmoscopy, has also helped us better understand the mechanism of damage to ocular tissues by external injuries.…”

mentioning

confidence: 99%

Editorial: Updates on Ocular Trauma

et al. 2022

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Activated Blood Coagulation Factor X (FXa) Contributes to the Development of Traumatic PVR Through Promoting RPE Epithelial-Mesenchymal Transition

Abstract: et al. Activated blood coagulation factor X (FXa) contributes to the development of traumatic PVR through promoting RPE epithelial-mesenchymal transition.

Cited by 7 publications

References 38 publications

Experimental Models to Study Epithelial-Mesenchymal Transition in Proliferative Vitreoretinopathy

Experimental Models to Study Epithelial-Mesenchymal Transition in Proliferative Vitreoretinopathy

Inhibition of EGFR attenuates EGF-induced activation of retinal pigment epithelium cell via EGFR/AKT signaling pathway

Editorial: Updates on Ocular Trauma

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