Base de dados : MEDLINE
Pesquisa : A11.329.228.109 [Categoria DeCS]
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[PMID]:28973326
[Au] Autor:Zhang Y; Kao WW; Hayashi Y; Zhang L; Call M; Dong F; Yuan Y; Zhang J; Wang YC; Yuka O; Shiraishi A; Liu CY
[Ad] Endereço:School of Optometry, Indiana University, Bloomington, Indiana, United States.
[Ti] Título:Generation and Characterization of a Novel Mouse Line, Keratocan-rtTA (KeraRT), for Corneal Stroma and Tendon Research.
[So] Source:Invest Ophthalmol Vis Sci;58(11):4800-4808, 2017 Sep 01.
[Is] ISSN:1552-5783
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Purpose: We created a novel inducible mouse line Keratocan-rtTA (KeraRT) that allows specific genetic modification in corneal keratocytes and tenocytes during development and in adults. Methods: A gene-targeting vector (Kera- IRES2-rtTA3) was constructed and inserted right after the termination codon of the mouse Kera allele via gene targeting techniques. The resulting KeraRT mouse was crossed to tet-O-Hist1H2B-EGFP (TH2B-EGFP) to obtain KeraRT/TH2B-EGFP compound transgenic mice, in which cells expressing Kera are labeled with green fluorescence protein (GFP) by doxycycline (Dox) induction. The expression patterns of GFP and endogenous Kera were examined in KeraRT/TH2B-EGFP. Moreover, KeraRT was bred with tet-O-TGF-α to generate a double transgenic mouse, KeraRT/tet-O-TGF-α, to overexpress TGF-α in corneal keratocytes upon Dox induction. Results: Strong GFP-labeled cells were detected in corneal stroma, limbs, and tail when KeraRT/TH2B-EGFP mice were fed Dox chow. There was no GFP in any single transgenic KeraRT or TH2B-EGFP mouse. Histological analysis showed that GFP in the cornea was limited to stromal keratocytes of KeraRT/TH2B-EGFP, which is consistent with Kera expression. Induction of GFP occurred in 24 hours and reached a plateau by 7 days after Dox induction. GFP could be detected 3-months after induction of KeraRT/TH2B-EGFP. Ectopic expression of TGF-α in corneal keratocytes caused hyperplasia in the corneal epithelium and stroma. Conclusions: The novel Dox inducible KeraRT driver mouse line is a useful genetic tool for gene manipulation and elucidating gene functions in corneal stroma and tendons of limbs and tail during embryonic development, homeostasis and pathogenesis.
[Mh] Termos MeSH primário: Substância Própria/metabolismo
Técnicas de Introdução de Genes
Camundongos Transgênicos/genética
Proteoglicanas/genética
Tendões/metabolismo
[Mh] Termos MeSH secundário: Animais
Ceratócitos da Córnea/metabolismo
Modelos Animais de Doenças
Epitélio Anterior/metabolismo
Técnicas de Inativação de Genes
Vetores Genéticos
Proteínas de Fluorescência Verde/metabolismo
Camundongos
Proteoglicanas/metabolismo
Fator de Crescimento Transformador alfa/genética
Fator de Crescimento Transformador alfa/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Kera protein, mouse); 0 (Proteoglycans); 0 (Transforming Growth Factor alpha); 147336-22-9 (Green Fluorescent Proteins)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171006
[Lr] Data última revisão:
171006
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171004
[St] Status:MEDLINE
[do] DOI:10.1167/iovs.17-22661


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[PMID]:28844046
[Au] Autor:Jiang Z; Liu G; Meng F; Wang W; Hao P; Xiang Y; Wang Y; Han R; Li F; Wang L; Li X
[Ad] Endereço:Clinical College of Ophthalmology, Tianjin Medical University, Tianjin, China.
[Ti] Título:Paracrine effects of mesenchymal stem cells on the activation of keratocytes.
[So] Source:Br J Ophthalmol;101(11):1583-1590, 2017 Nov.
[Is] ISSN:1468-2079
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:AIMS: The purpose of this study is to investigate the impact of mesenchymal stem cell (MSC)-derived soluble factors on the function of keratocytes, with a particular focus on the processes involved in wound healing, including keratocyte activation, migration and proliferation as well as extracellular matrix (ECM) synthesis. METHODS: Primary cultured rabbit keratocytes were treated with MSC-conditioned medium (MSC-CM). The paracrine factors released by bone marrow MSCs were examined by ELISA. Time-lapse microscope was used to examine wound closure in vitro. Mouse model of corneal injury was made by epithelial scraping after ethanol injury. RESULTS: MSC-CM significantly increased the wound closure rate of corneal stromal cells in vitro. This enhancement of wound closure by MSC-CM was due to the promotion of cell migration. MSC-CM enhanced keratocyte survival following ethanol injury via inhibiting apoptosis. The expression of ECM component genes in keratocytes was upregulated by MSC-CM. In addition, MSC-CM promoted corneal epithelial wound healing following chemical injury. A number of wound healing mediators were detected in MSC-CM, including vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), hepatocyte growth factor (HGF), transforming growth factor beta 1 (TGFß1), interleukin 8 (IL8), interleukin 6 (IL6) and monocyte chemoattractant protein 1 (MCP1). CONCLUSION: MSC secretes certain factors that accelerate corneal re-epithelialisation. The paracrine effects of MSC on corneal wound healing including improvements in cell viability, migration and ECM formation.
[Mh] Termos MeSH primário: Terapia Baseada em Transplante de Células e Tecidos/métodos
Lesões da Córnea/metabolismo
Ceratócitos da Córnea/patologia
Células Mesenquimais Estromais/metabolismo
Cicatrização
[Mh] Termos MeSH secundário: Animais
Sobrevivência Celular
Células Cultivadas
Lesões da Córnea/patologia
Lesões da Córnea/terapia
Ceratócitos da Córnea/metabolismo
Modelos Animais de Doenças
Ensaio de Imunoadsorção Enzimática
Matriz Extracelular/metabolismo
Células Mesenquimais Estromais/citologia
Coelhos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171102
[Lr] Data última revisão:
171102
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170828
[St] Status:MEDLINE
[do] DOI:10.1136/bjophthalmol-2016-310012


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[PMID]:28763562
[Au] Autor:Wang X; Majumdar S; Ma G; Sohn J; Yiu SC; Stark W; Al-Qarni A; Edward DP; Elisseeff JH
[Ad] Endereço:Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, Maryland, United States 2Translational Tissue Engineering Center, Johns Hopkins University, Baltimore, Maryland, United States.
[Ti] Título:Chondroitin Sulfate-Based Biocompatible Crosslinker Restores Corneal Mechanics and Collagen Alignment.
[So] Source:Invest Ophthalmol Vis Sci;58(10):3887-3895, 2017 Aug 01.
[Is] ISSN:1552-5783
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Purpose: To evaluate the crosslinking effect of functionalized chondroitin sulfate (CS) in an ex vivo rabbit cornea model. Methods: Chondroitin sulfate molecules were chemically modified with the N-hydroxysuccinimide (NHS) group. Enucleated rabbit eyes were crosslinked with 2, 5, or 10 mg/mL CS-NHS solution for 30 or 60 minutes. The CS-NHS penetration, corneal swelling ratio, Young's modulus, and ultrastructure of the crosslinked corneas were characterized. In addition, rabbit corneas were further treated with a collagenase-chondroitinase solution to create an ex vivo keratoconus (KC)-like model. The KC model corneas were crosslinked with a standard riboflavin-ultraviolet (UV) method or alternatively with CS-NHS. Corneal mechanics, ultrastructure, and keratocyte gene expression were evaluated after UV and CS-NHS crosslinking. Results: CS-NHS effectively penetrated into the corneal stroma within 60 minutes of treatment initiation. CS-NHS crosslinking reduced the swelling ratio by 35%, increased Young's modulus by 20%, and increased collagen fibril diameter and density. CS-NHS crosslinking improved corneal mechanics of KC model corneas to levels comparable to those with UV crosslinking. Moreover, CS-NHS crosslinking demonstrated significant downregulation of proinflammatory gene expression of keratocytes, indicating a potential protective effect imparted by CS-NHS during crosslinking. Conclusions: Our results demonstrated that CS-NHS can reinforce normal and KC model corneal mechanics, and restore collagen density and alignment in KC model corneas without causing extensive keratocyte apoptosis and proinflammatory gene upregulation. Therefore, CS-NHS crosslinking can potentially provide an effective, safe, and biocompatible means of corneal reinforcement.
[Mh] Termos MeSH primário: Sulfatos de Condroitina/farmacologia
Colágeno/metabolismo
Córnea/efeitos dos fármacos
Reagentes para Ligações Cruzadas/farmacologia
[Mh] Termos MeSH secundário: Animais
Fenômenos Biomecânicos
Córnea/metabolismo
Córnea/fisiopatologia
Ceratócitos da Córnea/efeitos dos fármacos
Ceratócitos da Córnea/metabolismo
Modelos Animais de Doenças
Módulo de Elasticidade/efeitos dos fármacos
Fármacos Fotossensibilizantes/farmacologia
Coelhos
Raios Ultravioleta
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cross-Linking Reagents); 0 (Photosensitizing Agents); 9007-28-7 (Chondroitin Sulfates); 9007-34-5 (Collagen)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170803
[Lr] Data última revisão:
170803
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170802
[St] Status:MEDLINE
[do] DOI:10.1167/iovs.16-21292


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[PMID]:28644862
[Au] Autor:Zhu Y; Reinach PS; Zhu H; Tan Q; Zheng Q; Qu J; Chen W
[Ad] Endereço:School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Zhejiang, China.
[Ti] Título:High-intensity corneal collagen crosslinking with riboflavin and UVA in rat cornea.
[So] Source:PLoS One;12(6):e0179580, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Corneal collagen cross-linking (CXL) halts human corneal ectasias progression by increasing stromal mechanical stiffness. Although some reports describe that this procedure is effective in dealing with some infectious and immunologic corneal thinning diseases, there is a need for more animal models whose corneal thickness more closely resemble those occurring in these patients. To meet this need, we describe here high-intensity protocols that are safe and effective for obtaining CXL in rat corneas. Initially, a range of potentially effective UVA doses were evaluated based on their effectiveness in increasing tissue enzymatic resistance to dissolution. At UVA doses higher than a threshold level of 0.54 J/cm2, resistance to enzymatic digestion increased relative to that in non-irradiated corneas. Based on the theoretical threshold CXL dose, a CXL regimen was established in which the UVA tissue irradiance was 9 mW/cm2, which was delivered at doses of either 2.16, 2.7 or 3.24 J/cm2. Their dose dependent effects were evaluated on ocular surface morphological integrity, keratocyte apoptotic frequency, tissue thickness and endothelial cell layer density. Doses of 2.16 and 2.7 J/cm2 transiently decreased normal corneal transparency and increased thickness. These effects were fully reversed after 14 days. In contrast, 3.24 J/cm2 had more irreversible side effects. Three days after treatment, apoptotic frequency in the CXL-2.16 group was lower than that at higher doses. Endothelial cell losses remained evident only in the CXL-3.24 group at 42 days posttreatment. Stromal fiber thickening was evident in all the CXL-treated groups. We determined both the threshold UVA dose using the high-intensity CXL procedure and identified an effective dose range that provides optimal CXL with minimal transient side effects in the rat cornea. These results may help to provide insight into how to improve the CXL outcome in patients afflicted with a severe corneal thinning disease.
[Mh] Termos MeSH primário: Colágeno/metabolismo
Córnea/efeitos dos fármacos
Córnea/efeitos da radiação
Reagentes para Ligações Cruzadas/farmacologia
Riboflavina/farmacologia
Terapia Ultravioleta
[Mh] Termos MeSH secundário: Animais
Apoptose/efeitos dos fármacos
Apoptose/efeitos da radiação
Córnea/metabolismo
Córnea/patologia
Ceratócitos da Córnea/efeitos dos fármacos
Ceratócitos da Córnea/metabolismo
Ceratócitos da Córnea/patologia
Ceratócitos da Córnea/efeitos da radiação
Relação Dose-Resposta à Radiação
Células Endoteliais/efeitos dos fármacos
Células Endoteliais/metabolismo
Células Endoteliais/efeitos da radiação
Células Endoteliais/ultraestrutura
Marcação In Situ das Extremidades Cortadas
Masculino
Microscopia Confocal
Microscopia Eletrônica de Transmissão
Modelos Animais
Tamanho do Órgão
Distribuição Aleatória
Ratos Sprague-Dawley
Tomografia de Coerência Óptica
Raios Ultravioleta
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cross-Linking Reagents); 9007-34-5 (Collagen); TLM2976OFR (Riboflavin)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171002
[Lr] Data última revisão:
171002
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170624
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0179580


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[PMID]:28599847
[Au] Autor:Sriram S; Tran JA; Guo X; Hutcheon AEK; Kazlauskas A; Zieske JD
[Ad] Endereço:The Schepens Eye Research Institute/Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA. Electronic address: Sriniwas_Sriram@meei.harvard.edu.
[Ti] Título:Development of wound healing models to study TGFß3's effect on SMA.
[So] Source:Exp Eye Res;161:52-60, 2017 Aug.
[Is] ISSN:1096-0007
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The goal of this study was to test the efficacy of transforming growth factor beta 3 (TGFß3) in reducing α-smooth muscle actin (SMA) expression in two models-an ex vivo organ culture and an in vitro 3D cell construct-both of which closely mimic an in vivo environment. For the ex vivo organ culture system, a central 6.0 mm corneal keratectomy was performed on freshly excised rabbit globes The corneas were then excised, segregated into groups treated with 1.0 ng/ml TGFß1 or ß3 (T1 or T3, respectively), and cultured for 2 weeks. The corneas were assessed for levels of haze and analyzed for SMA mRNA levels. For the 3D in vitro model, rabbit corneal fibroblasts (RbCFs) were cultured for 4 weeks on poly-transwell membranes in Eagle's minimum essential media (EMEM) + 10% FBS + 0.5 mM vitamin C ± 0.1 ng/ml T1 or T3. At the end of 4 weeks, the constructs were processed for analysis by indirect-immunofluorescence (IF) and RT-qPCR. The RT-qPCR data showed that SMA mRNA expression in T3 samples for both models was significantly lower (p < 0.05) than T1 treatment (around 3-fold in ex vivo and 2-fold in constructs). T3 also reduced the amount of scarring in ex vivo corneas as compared with the T1 samples. IF data from RbCF constructs confirmed that T3-treated samples had up to 4-fold (p < 0.05) lower levels of SMA protein expression than samples treated with T1. These results show that T3 when compared to T1 decreases the expression of SMA in both ex vivo organ culture and in vitro 3D cell construct models. Understanding the mechanism of T3's action in these systems and how they differ from simple cell culture models, may potentially help in developing T3 as an anti-scarring therapy.
[Mh] Termos MeSH primário: Actinas/genética
Córnea/efeitos dos fármacos
Ceratócitos da Córnea/efeitos dos fármacos
Modelos Animais de Doenças
Fator de Crescimento Transformador beta3/farmacologia
Cicatrização/fisiologia
[Mh] Termos MeSH secundário: Animais
Técnicas de Cultura de Células
Córnea/metabolismo
Ceratócitos da Córnea/metabolismo
Substância Própria/citologia
Técnica Indireta de Fluorescência para Anticorpo
Técnicas de Cultura de Órgãos
Fator de Crescimento Derivado de Plaquetas/metabolismo
RNA Mensageiro/genética
Coelhos
Reação em Cadeia da Polimerase em Tempo Real
Fator de Crescimento Transformador beta1/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Actins); 0 (Platelet-Derived Growth Factor); 0 (RNA, Messenger); 0 (Transforming Growth Factor beta1); 0 (Transforming Growth Factor beta3)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170902
[Lr] Data última revisão:
170902
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170611
[St] Status:MEDLINE


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[PMID]:28418498
[Au] Autor:Kimura K; Zhou H; Orita T; Kobayashi M; Nishida T; Sonoda KH
[Ad] Endereço:Department of Ophthalmology, Yamaguchi University Graduate School of Medicine, Ube City, Yamaguchi, Japan.
[Ti] Título:Suppression by an RAR-γ Agonist of Collagen Degradation Mediated by Corneal Fibroblasts.
[So] Source:Invest Ophthalmol Vis Sci;58(4):2250-2257, 2017 Apr 01.
[Is] ISSN:1552-5783
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Purpose: To examine the role of retinoic acid receptor (RAR) isoforms in interleukin-1ß (IL-1ß)-induced collagen degradation by corneal fibroblasts. Methods: Primary rabbit corneal fibroblasts embedded in a three-dimensional collagen gel were incubated with or without all-trans retinoic acid (ATRA), the RAR-α agonist Am580, the RAR-ß agonist AC55649, or the RAR-γ agonist R667. Collagen degradation was determined by measurement of hydroxyproline produced in acid hydrolysates of culture supernatants. Matrix metalloproteinase (MMP) expression was evaluated by immunoblot analysis and gelatin zymography. The phosphorylation of mitogen-activated protein kinases (MAPKs) and the endogenous nuclear factor (NF)-κB inhibitor IκB-α was examined by immunoblot analysis. Cell proliferation was measured with a bromodeoxyuridine incorporation assay, and cell viability was determined by measurement of the release of lactate dehydrogenase. Results: Interleukin-1ß-induced collagen degradation by corneal fibroblasts was inhibited by ATRA, Am580, and R667 in a concentration-dependent manner but was unaffected by AC55649, with the inhibitory effects of ATRA and R667 being markedly greater than that of Am580. The IL-1ß-induced production of MMP-1, MMP-2, MMP-3, and MMP-9 by corneal fibroblasts was also inhibited by R667 in a concentration-dependent manner. R667 inhibited the IL-1ß-induced phosphorylation of IκB-α but not that of MAPKs. R667 had no effect on the proliferation or viability of corneal fibroblasts. Conclusions: The RAR-γ agonist R667 suppressed MMP production and thereby inhibited collagen degradation by corneal fibroblasts exposed to the proinflammatory cytokine IL-1ß. These effects of R667 may be mediated by the NF-κB signaling pathway.
[Mh] Termos MeSH primário: Benzoatos/farmacologia
Compostos de Bifenilo/farmacologia
Colágeno/metabolismo
Ceratócitos da Córnea/efeitos dos fármacos
Pirazóis/farmacologia
Receptores do Ácido Retinoico/agonistas
Tetra-Hidronaftalenos/farmacologia
[Mh] Termos MeSH secundário: Animais
Proliferação Celular/efeitos dos fármacos
Sobrevivência Celular/efeitos dos fármacos
Córnea/citologia
Córnea/efeitos dos fármacos
Córnea/metabolismo
Ceratócitos da Córnea/citologia
Ceratócitos da Córnea/metabolismo
Relação Dose-Resposta a Droga
Immunoblotting
Interleucina-1beta/farmacologia
Masculino
Coelhos
Tretinoína/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (4'-octyl-4-biphenylcarboxylic acid); 0 (Benzoates); 0 (Biphenyl Compounds); 0 (Interleukin-1beta); 0 (Pyrazoles); 0 (R667 compound); 0 (Receptors, Retinoic Acid); 0 (Tetrahydronaphthalenes); 0 (retinoic acid receptor gamma); 102121-60-8 (Am 580); 5688UTC01R (Tretinoin); 9007-34-5 (Collagen)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170426
[Lr] Data última revisão:
170426
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170419
[St] Status:MEDLINE
[do] DOI:10.1167/iovs.15-18701


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[PMID]:28384032
[Au] Autor:Fernández-Ferreiro A; Santiago-Varela M; Gil-Martínez M; González-Barcia M; Luaces-Rodríguez A; Díaz-Tome V; Pardo M; Méndez JB; Piñeiro-Ces A; Rodríguez-Ares MT; Lamas MJ; Otero-Espinar FJ
[Ad] Endereço:1 Department Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Santiago de Compostela (USC) , Santiago de Compostela, Spain .
[Ti] Título:In Vitro Evaluation of the Ophthalmic Toxicity Profile of Chlorhexidine and Propamidine Isethionate Eye Drops.
[So] Source:J Ocul Pharmacol Ther;33(3):202-209, 2017 Apr.
[Is] ISSN:1557-7732
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:PURPOSE: Acanthamoeba keratitis causes frequent epithelial lesions that fully expose the corneal stroma. The aim of this study was to determine the toxic profile of chlorhexidine and propamidine eye drops. METHODS: We used primary human keratocytes in cell culture in combination with a novel technology that evaluates dynamic real-time cytotoxicity through impedance analysis. Additional studies such as a classic cell viability test (WST-1 ), a bovine corneal opacity and permeability assay, and an irritation eye study (Hen's Egg Test [HET]) have been made. RESULTS: Both eye drop formulations showed a time- and concentration-dependent toxicity profile, in which long periods and high concentrations were more detrimental to cells. In prolonged times of exposure, propamidine is more harmful to cells than chlorhexidine. On the contrary, no irritation has been detected in using the HET-chorioallantoic membrane test and no alterations in the corneal transparency nor permeability was produced by the treatment with both eye drops. CONCLUSIONS: In culture assay, chlorhexidine eye drops have proven to be less cytotoxic than Brolene for a long contact period of time, but no signs of irritation or alterations in transparency or permeability have been observed in the cornea after both treatments.
[Mh] Termos MeSH primário: Benzamidinas/toxicidade
Clorexidina/toxicidade
Ceratócitos da Córnea/efeitos dos fármacos
Soluções Oftálmicas/toxicidade
[Mh] Termos MeSH secundário: Alternativas aos Testes com Animais
Animais
Benzamidinas/administração & dosagem
Bovinos
Sobrevivência Celular/efeitos dos fármacos
Células Cultivadas
Química Farmacêutica
Clorexidina/administração & dosagem
Córnea/efeitos dos fármacos
Relação Dose-Resposta a Droga
Olho/efeitos dos fármacos
Seres Humanos
Soluções Oftálmicas/administração & dosagem
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Benzamidines); 0 (Ophthalmic Solutions); 7T9IJ84C42 (propamidine isethionate); R4KO0DY52L (Chlorhexidine)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171110
[Lr] Data última revisão:
171110
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170407
[St] Status:MEDLINE
[do] DOI:10.1089/jop.2016.0053


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[PMID]:28257425
[Au] Autor:Hertsenberg AJ; Shojaati G; Funderburgh ML; Mann MM; Du Y; Funderburgh JL
[Ad] Endereço:Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States.
[Ti] Título:Corneal stromal stem cells reduce corneal scarring by mediating neutrophil infiltration after wounding.
[So] Source:PLoS One;12(3):e0171712, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Corneal scarring limits vision for millions of individuals worldwide. Corneal transplantation (keratoplasty) is the standard of care for corneal opacity; however, it bears the risk of graft rejection and infection and is not universally available. Stem cell therapy holds promise as an alternative to keratoplasty. Stem cells from human corneal stroma (CSSC) induce regeneration of transparent corneal tissue in a mouse wound-healing model. In this study we investigated the mechanism by which CSSC prevent deposition of fibrotic tissue. Infiltration by CD11b+/Ly6G+ neutrophils and myeloperoxidase expression were increased in corneas 24 hr after corneal wounding but were reduced in CSSC-treated wounds. Secretion of TSG-6, a protein known to regulate neutrophil migration, was up-regulated in CSSC in response to TNFα and as CSSC differentiate to keratocytes. In vivo, wounded mouse corneas treated with CSSC contained human TSG-6. Inhibition of neutrophil infiltration into cornea by CSSC was reversed when TSG-6 expression was knocked down using siRNA. Silencing of TSG-6 expression in CSSC reduced their ability to block scarring and the expression of mRNA for fibrosis-associated proteins collagen III, tenascin C, and smooth muscle actin in wounded corneas. Neutropenic mice exhibited a significant reduction in corneal scarring and fibrotic mRNA expression 2 weeks after wounding. These results support the conclusion that neutrophil infiltration is an essential event in the fibrotic response to corneal damage and that prevention of scarring by CSSC is mediated by secretion of TSG-6 by these cells.
[Mh] Termos MeSH primário: Lesões da Córnea/terapia
Ceratócitos da Córnea/transplante
Substância Própria/transplante
Transplante de Células-Tronco
[Mh] Termos MeSH secundário: Animais
Moléculas de Adesão Celular/genética
Córnea/metabolismo
Córnea/fisiopatologia
Lesões da Córnea/fisiopatologia
Substância Própria/fisiopatologia
Transplante de Córnea
Rejeição de Enxerto/fisiopatologia
Seres Humanos
Camundongos
Infiltração de Neutrófilos/genética
Regeneração/genética
Cicatrização
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cell Adhesion Molecules); 0 (Tnfaip6 protein, mouse)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170822
[Lr] Data última revisão:
170822
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170304
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0171712


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[PMID]:28192588
[Au] Autor:Jhanji V; Chan TC; Li WY; Lim RR; Yu MC; Law K; Yi P; Yip YW; Wang Y; Ng TK; Chaurasia SS; Mohan RR
[Ti] Título:Conventional Versus Inverted Side-cut Flaps for Femtosecond Laser-Assisted LASIK: Laboratory and Clinical Evaluation.
[So] Source:J Refract Surg;33(2):96-103, 2017 Feb 01.
[Is] ISSN:1081-597X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:PURPOSE: To study the differences in early corneal cellular events and biomechanical properties after femtosecond laser-assisted LASIK performed using conventional or inverted side-cut angles. METHODS: In the laboratory study, left eyes of 24 rabbits underwent LASIK flap creation with a 70° or 115° side-cut. The contralateral eyes served as controls. The corneas were harvested 24 hours postoperatively. In the clinical study, 2 eyes of each patient (n = 29) were randomized to corneal flap creation with 70° or 115° side-cut angles during LASIK. The Ocular Response Analyzer (ORA; Reichert Ophthalmic Instruments, Depew, NY) was used to assess biomechanical properties of the cornea. RESULTS: In rabbit eyes, epithelial ingrowth was observed more frequently in flaps with 70° side cuts compared to flaps with 115° side-cuts. Corneas with 70° side-cuts showed significantly increased apoptotic cells compared to 115° side-cuts in the central (P = .001) and peripheral (P = .004) regions. Fifty-eight eyes of 29 patients were included in the clinical study. An overall reduction in Goldmann-correlated intraocular pressure, corneal-compensated intraocular pressure, corneal resistance factor, corneal hysteresis measurements, p1 area, p2 area, and p1 area 1 and p2 area 1 was noted 37 ± 2 months after surgery (P < .001). No significant difference was observed in the change of any of these parameters between both groups (P ≥ .146). CONCLUSIONS: Significant differences in wound healing were observed in rabbit corneas that underwent LASIK with conventional or inverted side-cuts. Variation in flap side-cut angles did not alter the long-term biomechanical properties measured with the ORA in patients after LASIK. [J Refract Surg. 2017;33(2):96-103.].
[Mh] Termos MeSH primário: Substância Própria/cirurgia
Ceratomileuse Assistida por Excimer Laser In Situ/métodos
Lasers de Excimer/uso terapêutico
Miopia/cirurgia
Retalhos Cirúrgicos
Cicatrização/fisiologia
[Mh] Termos MeSH secundário: Adulto
Animais
Apoptose
Fenômenos Biomecânicos
Antígeno CD11b/metabolismo
Ceratócitos da Córnea/patologia
Feminino
Técnica Indireta de Fluorescência para Anticorpo
Seres Humanos
Marcação In Situ das Extremidades Cortadas
Pressão Intraocular/fisiologia
Antígeno Ki-67/metabolismo
Masculino
Meia-Idade
Miopia/metabolismo
Miopia/fisiopatologia
Coelhos
Acuidade Visual/fisiologia
Adulto Jovem
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (CD11b Antigen); 0 (Ki-67 Antigen)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170214
[St] Status:MEDLINE
[do] DOI:10.3928/1081597X-20161102-02


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[PMID]:28118663
[Au] Autor:Yim B; Park JH; Jeong H; Hong J; Shin YJ; Chuck RS; Park CY
[Ad] Endereço:Department of Ophthalmology, Dongguk University, Ilsan Hospital, Goyang, South Korea.
[Ti] Título:The Effects of Nonporous Silica Nanoparticles on Cultured Human Keratocytes.
[So] Source:Invest Ophthalmol Vis Sci;58(1):362-371, 2017 Jan 01.
[Is] ISSN:1552-5783
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Purpose: Silica nanoparticles (SiNPs) are promising carriers for ophthalmic drug delivery. In this study, we investigated the effect of various sizes of nonporous SiNPs on cultured human keratocytes. Methods: Three different sizes of SiNPs (50, 100, and 150 nm) were manufactured. Primarily cultured human keratocytes were exposed to different concentrations (0, 25, 50, and 100 µg/mL) of three sizes of SiNPs for up to 72 hours. Intracellular reactive oxygen species (ROS) generation, cellular viability, lactate dehydrogenase (LDH) assay, autophagy, vimentin expression, and mammalian target of rapamycin (mTOR) pathway activation were evaluated. Intracellular distribution of SiNPs was evaluated with transmission electron microscopy. Results: Transmission electron microscopy revealed SiNPs were taken up by keratocytes inside cytoplasmic vacuoles. Neither nuclear entry of SiNPs nor mitochondrial structural damage was observed. Both intracellular ROS generation and LDH level remained unchanged with up to 100 µg/mL SiNP treatment. Cellular viability was not affected by SiNP treatment. Autophagy showed significant dose-dependent activation with 50- and 100-nm SiNPs. However, mTOR activation remained unchanged. Vimentin expression did not show any significant increase with SiNPs. Conclusions: Our findings suggested that 50-, 100-, and 150-nm SiNPs did not induce significant cytotoxicity in cultured human keratocytes at concentrations up to 100 µg/mL.
[Mh] Termos MeSH primário: Ceratócitos da Córnea/efeitos dos fármacos
Nanopartículas
Dióxido de Silício/farmacologia
[Mh] Termos MeSH secundário: Animais
Autofagia
Western Blotting
Contagem de Células
Sobrevivência Celular
Células Cultivadas
Ceratócitos da Córnea/metabolismo
Ceratócitos da Córnea/ultraestrutura
Modelos Animais de Doenças
Feminino
Seres Humanos
Imuno-Histoquímica
L-Lactato Desidrogenase/metabolismo
Masculino
Microscopia Eletrônica de Transmissão
Tamanho da Partícula
Ratos
Ratos Sprague-Dawley
Espécies Reativas de Oxigênio/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Reactive Oxygen Species); 7631-86-9 (Silicon Dioxide); EC 1.1.1.27 (L-Lactate Dehydrogenase)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170621
[Lr] Data última revisão:
170621
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170125
[St] Status:MEDLINE
[do] DOI:10.1167/iovs.16-20603



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