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1.
Regen Med ; 15(10): 2163-2179, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33315474

RESUMO

Aim: To assess the safety and feasibility of subtenon transplantation of human placenta-derived mesenchymal stem cells (hPMSCs) in Asian patients with traumatic optic neuropathy. Materials & methods: The survival of retinal ganglion cells in the rat retina was evaluated by monitoring the expression of Tuj1 and Gfap after optic nerve compression. Based on the preclinical data, we conducted a Phase I, open label, single center, nonrandomized clinical trial in four Asian traumatic optic neuropathy patients. The safety and ophthalmologic changes were evaluated. Results: The levels of Tuj1 and Gfap expression were significantly increased in the hPMSC treatment group compared with the sham group, suggesting a protective effect of hPMSCs on the optic nerve and retinal ganglion cells. There was no evidence of adverse proliferation, tumorigenicity, severe inflammation or other serious issues during the 12-month follow-up period. Visual acuity improved in all four patients. Conclusion: The results suggested that hPMSCs are safe and have potential utility in regenerative medicine. Clinical trial registration number: 20150196587 (Korean FDA), 2015-07-123-054 (IRB).

2.
Stem Cell Res Ther ; 11(1): 469, 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33153489

RESUMO

BACKGROUND: Placenta-derived mesenchymal stem cells (PD-MSCs) have unique immunomodulatory properties. Phosphatase of regenerating liver-1 (PRL-1) regulates the self-renewal ability of stem cells and promotes proliferation. Graves' ophthalmopathy (GO) is an autoimmune inflammatory disease of the orbit and is characterized by increased orbital levels of adipose tissue. Here, we evaluated the therapeutic mechanism for regulation of adipogenesis by PRL-1-overexpressing PD-MSCs (PD-MSCsPRL-1, PRL-1+) in orbital fibroblast (OF) with GO patients. METHODS: PD-MSCs isolated from human placenta were transfected with the PRL-1 gene using nonviral transfection method. Primary OFs were isolated from orbital adipose tissue specimens from GO patients. After maturation as adipogenic differentiation, normal and GO-derived OFs were cocultured with naïve and PD-MSCsPRL-1. We analyzed the protein levels of adipogenesis markers and their signaling pathways in OFs from GO patients. RESULTS: The characteristics of PD-MSCsPRL-1 were similar to those of naïve cells. OFs from GO patients induced adipocyte differentiation and had significantly decreased a lipid accumulation after coculture with PD-MSCsPRL-1 compared to naïve cells. The mRNA and protein expression of adipogenic markers was decreased in PD-MSCsPRL-1. Insulin-like growth factor-binding proteins (IGFBPs) secreting PD-MSCsPRL-1 downregulated the phosphorylated PI3K/AKT/mTOR expression in OFs from GO patients. Interestingly, IGFBP2, - 4, - 6, and - 7 expression in PD-MSCsPRL-1, which was mediated by integrin alpha 4 (ITGA4) and beta 7 (ITGB7), was higher than that in naïve cells and upregulated phosphorylated FAK downstream factor. CONCLUSION: In summary, IGFBPs secreting PD-MSCPRL-1 inhibit adipogenesis in OFs from GO patients by upregulating phosphorylated FAK and downregulating PI3K/AKT/mTOR signaling pathway. The functional enhancement of PD-MSCs by nonviral gene modification provides a novel therapeutic strategy for the treatment of degenerative diseases.

3.
BJR Open ; 2(1): 20200013, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33178975

RESUMO

Objective: To evaluate the safety and effectiveness of hypofractionated orbital radiotherapy applied in the treatment of thyroid-associated ophthalmopathy (TAO) patients. Methods: Between 2014 and 2018, we retrospectively reviewed the cases of 28 patients with TAO. All patients underwent radiotherapy on both retroocular tissues and received an oral steroid. Patients were divided into two treatment groups: 14 patients received conventional fractionated radiotherapy (20 Gy in 10 fractions), and the second group of 14 patients received hypofractionated radiotherapy (20 Gy in five fractions). The clinical activity score (CAS), NOSPECS (No physical signs or symptoms, Only signs, Soft tissue involvement, Proptosis, Extraocular muscle signs, Corneal involvement, and Sight loss) classification, Hess screen test and binocular single vision (BSV) were evaluated to determine the response to treatment before and at 1 month after radiotherapy. Results: There were no significant differences in any of the variables between the two treatment groups. In both groups, the CAS and NOSPECS score decreased significantly, and the range of extraocular muscle motility in Hess screen test and BSV improved significantly after radiotherapy (p < 0.05). There were no significant differences in CAS, NOSPECS score, Hess screen test or BSV between the two groups. No radiation-related, acute severe toxicity was observed. Conclusion: Hypofractionated radiotherapy for TAO produced a comparable clinical outcome to that of conventional fractionated radiotherapy. Further case accumulation and long-term follow-up are required to determine if late toxicity occurs and to confirm efficacy. Advances in knowledge: This is the first study to show that the efficacy and risk of adverse events are comparable between hypofractionated radiotherapy and conventional radiotherapy in the treatment of TAO.

4.
Stem Cell Res Ther ; 11(1): 428, 2020 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-33008487

RESUMO

BACKGROUND: Stem cell transplantation has been proposed as an alternative treatment for intractable optic nerve disorders characterized by irrecoverable loss of cells. Mesenchymal stem cells, with varying tissue regeneration and recovery capabilities, are being considered for potential cell therapies. To overcome the limitations of cell therapy, we isolated exosomes from human placenta-derived mesenchymal stem cells (hPMSCs) and investigated their therapeutic effects in R28 cells (retinal precursor cells) exposed to CoCl2. METHOD: After 9 h of exposure to CoCl2, the hypoxic damaged R28 cells were divided into the non-treatment group (CoCl2 + R28 cells) and treatment group (CoCl2 + R28 cells treated with exosome). Immunoblot analysis was performed for Pcna, Hif-1α, Vegf, Vimentin, Thy-1, Gap43, Ermn, Neuroflament, Wnt3a, ß-catenin, phospo-GSK3ß, Lef-1, UBA2, Skp1, ßTrcp, and ubiquitin. The proteomes of each group were analyzed by liquid chromatography/tandem mass (LC-MS/MS) spectrometry. Differentially expressed proteins (DEPs) were detected by label-free quantification, and the interactions of the proteins were examined through signal transduction pathway and gene ontology analysis. RESULT: We observed that exosome could significantly recover proliferation damaged by CoCl2 treatment. In addition, the treatment group presented the decreased expression of Hif-1α protein (P < 0.05) and increased expression of proliferation marker, Pcna, and nerve regeneration-related factors such as Vimentin, Thy-1, and Neuroflament (P < 0.05) compared with the non-treatment group. In total, 200 DEPs were identified in the non-treatment group and treatment group (fold change ≥ 2, p < 0.05). Catenin and ubiquitin systems (UBA2, UBE2E3, UBE2I) were found in both the DEP lists of downregulated proteins from the non-treatment group and upregulated proteins from the treatment group. The mRNA expressions of ubiquitin systems were significantly decreased under hypoxic conditions. Moreover, UBA2 and Wnt/ß-catenin protein were associated with the rescue of the hypoxic damaged R28 cells. Using a siRNA system, we could find it out that hPMSC exosomes could not repair altered expressions of target proteins by CoCl2 in lacking UBA2 R28 cells. CONCLUSION: This study reported that hypoxic damaged expression of regeneration markers in R28 cells was significantly recovered by hPMSC exosomes. We could also demonstrate that UBA2 played a key role in activating the Wnt/ß-catenin signaling pathway during protection of hypoxic damaged R28 cells, induced by hPMSC exosomes.

5.
Artigo em Inglês | MEDLINE | ID: mdl-32743774

RESUMO

BACKGROUND: To investigate the lacrimal drainage system (LDS) from the punctum to the inferior meatus and the clinical outcomes of transcanalicular endoscopic dacryoplasty and silicone intubation through dacryoendoscopy in patients with primary acquired nasolacrimal duct obstruction (PANDO). METHODS: We conducted a retrospective chart review of 203 cases from 156 patients who underwent dacryoendoscopy (FT-203F; Fibertech Co., Tokyo, Japan) and sheath-guided silicone intubation for PANDO from December 2014 to March 2018. Clinical characteristics, tear meniscus height, irrigation test, dacryocystographic findings, and dacryoendoscopic findings related to clinical factors and surgical outcomes were evaluated. RESULTS: The study population consisted of 44 males and 119 females (mean age, 60.4 ± 13.6 years). The mean epiphora duration was 3.8 ± 4.8 years. Dacryoendoscopic findings revealed that the following factors were associated with LDS obstruction (% cases): mucus, 39.9%; fibrotic membrane, 19.2%; stones, 9.4%; granulation, 8.9%; and stenosis, 2.7%. The locations of obstruction were as follows (% cases): nasolacrimal duct, 35.7%; canaliculus, 33.0%; sac, 27.6%; and inferior meatus, 3.5%. The types of LDS obstruction were classified into two groups: secretory group (n = 118) that included mucus, stones, and granulation, and structural group (n = 85) associated with the membrane and stenosis; the pattern of them was divided into focal (n = 134) and diffuse (n = 76). The overall success rate was 86.2%. The success rate of the structural group (95.3%) was significantly higher than that of the secretory group (79.7%) (p = 0.001). All membranous obstruction cases at the inferior meatus were treated successfully, regardless of the irrigation test results. The success rate of the focal group (93.1%) was significantly higher than that of the diffuse group (74.0%) (p = 0.003). CONCLUSIONS: Dacryoendoscopic findings were informative regarding the clinical factors leading to LDS in PANDO patients. Mucus and stones in the lacrimal sac were common findings of functional lacrimal duct obstruction. Membranous obstruction and stenosis could be managed by recanalization under direct visualization. Transcanalicular endoscopic dacryoplasty and silicone intubation is considered to be a safe and effective procedure, sparing the patient from bony destruction in selected cases of PANDO.

6.
Mol Neurobiol ; 57(8): 3362-3375, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32524519

RESUMO

Human placenta-derived stem cells (hPSCs) with the therapeutic potential to recover from optic nerve injury have been reported. We have recently demonstrated that hPSCs have protective abilities against hypoxic damage. To improve the capacity of hPSCs, we established a hypoxia-preconditioned strain (HPPCs) using a hypoxic chamber. The hPSCs were exposed to short-term hypoxic conditions of 2.2% O2 and 5.5% CO2. We also performed in vivo experiments to demonstrate the recovery effects of HPPCs using an optic nerve injury rat model. Naïve hPSCs (and HPPCs) were injected into the optic nerve. After 1, 2, or 4 weeks, we analyzed changes in target proteins in the optic nerve tissues. In the retina, GAP43 expression was higher in both groups of naïve hPSCs and HPPCs versus sham controls. Two weeks after injection, all hPSC-injected groups showed recovery of tuj1 expression in damaged retinas. We also determined GFAP expression in retinas using the same model. In optic nerve tissues, HIF-1α levels were significantly lower in the HPPC-injected group 1 week after injury, and Thy-1 levels were higher in the hPSC-injected group at 4 weeks. There was also an enhanced recovery of Thy-1 expression after HPPC injection. In addition, R28 cells exposed to hypoxic conditions showed improved viability through enhanced recovery of HPPCs than naïve hPSCs. VEGF protein was a mediator in the recovery pathway via upregulation of target proteins regulated by HPPCs. Our results suggest that HPPCs may be candidates for cell therapy for the treatment of traumatic optic nerve injury.

7.
Stem Cells Dev ; 29(6): 353-363, 2020 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-31969085

RESUMO

Mesenchymal stem cells (MSCs) are useful for various purposes, including tissue engineering, regeneration, and gene therapy. MSCs isolated from extraocular muscles (EOMs) can be easily expanded in vitro, and can undergo multilineage differentiations involving adipogenesis, chondrogenesis, osteogenesis, and even neuronal or myogenic differentiation. This study aimed to isolate, characterize, and compare extraocular muscle-derived muscle progenitor cells (EOM-MPCs) from normal subjects and patients with Graves' orbitopathy (GO). EOM was obtained during strabismus surgery. Flow cytometry was conducted to identify CD surface antigens such as CD34, CD45, CD44, CD59, CD73, and CD90. We quantitated various cytokines secreted from MSCs, including interleukin (IL)-1α, IL-2, IL-6, IL-8, IL-10, IL-12, IL17A, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ, using a multi-analysis enzyme-linked immunosorbent assay array kit. We performed Oil Red O staining for adipogenesis, Alzarin Red staining for osteogenesis, Alcian blue staining for chondrogenesis, and polymerase chain reaction to measure messenger RNA expression during myogenesis. Our results show that EOM-MPCs from normal subjects and GO patients had similar levels of surface antigen expression and cytokine secretion. There was also no significant difference in the multilineage differentiation of adipocytes, chondrocytes, osteocytes, and myoblasts from EOM-MPCs taken from normal subjects and GO patients. However, hyaluronic acid synthetase 2 expression was higher after induction with tafluprost in EOM-MPCs from GO patients when compared with normal subjects. Together, these results show that EOM-MPCs derived from normal subjects are a good source for stem cell-based therapy for various disorders.

8.
J Craniofac Surg ; 31(1): 271-273, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31794448

RESUMO

PURPOSE: Hyaluronic acid gel (HAG) fillers provide a versatile and safe correction method for a sunken superior sulcus (SS) resulting from soft tissue volume loss occurring with aging, previous surgery, or enophthalmos related to trauma or phthisis bulbi. The purpose of this study was to report the long-term clinical outcomes of filler injection for soft-tissue augmentation in patients with a deep SS. DESIGN: Retrospective, interventional case series METHODS:: The medical records of 27 patients (32 eyes) with deep superior sulci were reviewed. Twenty injections of hyaluronic acid fillers (Restylane; Q-med AB, Uppsala, Sweden) were performed in the retrobulbar (RB) area, and 15 injections were performed in the SS. Pre- and post-treatment photographs were taken. MAIN OUTCOMES MEASURES: Visual acuity for seeing eyes, intraocular pressure, exophthalmos measurement, marginal reflex distance 1, interpalpebral fissure, tarsal platform show, and SS hollowing depth grade RESULTS:: Enophthalmos corrections were 1.3 ±â€Š0.8 mm (P < 0.001) and the SS hollowing grade decrease was 1.2 ±â€Š0.9 (P < 0.01) after 1 month of RB injection. Enophthalmos corrections were 0.1 ±â€Š0.4 mm (P = 0.317) and the SS sunkeness grade decrease was 1.7 ±â€Š0.8 (P < 0.001) after 1 month of SS injection. The amount of filler to correct enophthalmos of 1 mm was 0.83 ±â€Š0.53 mL using the RB injection. Using Kaplan-Meier survival analysis, the mean period of maintenance for deep SS correction was 9.1 months for RB injections and 8.5 months for SS injections. CONCLUSION: Retrobulbar (RB) hyaluronic acid gel (HAG) injections corrected enophthalmos and a deep SS, while SS injections corrected only a deep SS. These 2 techniques of RB and direct sulcus injection are safe and effective methods for the correction of a deep SS.


Assuntos
Enoftalmia/tratamento farmacológico , Olho , Ácido Hialurônico/análogos & derivados , Órbita , Adulto , Feminino , Géis , Humanos , Ácido Hialurônico/administração & dosagem , Ácido Hialurônico/uso terapêutico , Injeções , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
9.
Graefes Arch Clin Exp Ophthalmol ; 258(1): 201-207, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31713749

RESUMO

PURPOSE: We investigated the etiology of punctal stenosis based on the histopathological features of puncta and clinical correlations in punctal stenosis patients. METHODS: A retrospective review was conducted of 69 cases from 38 patients who were diagnosed with punctal stenosis. Slit-lamp examination, the lacrimal irrigation test, dacryocystography, and spectral domain-optical coherence tomography were performed for the evaluation of punctal occlusions. For treatment, punctoplasty using a punch biopsy with or without silicone tube insertion and histopathological examinations were performed. RESULTS: The pathological features of the punctal membranes were classified into two types of epithelia: squamous (95.7%, 66/69) and columnar (4.3%, 3/69). The squamous epithelial specimens were divided into three groups: fibrous tissue (66.8%, 48/69), goblet cells (21.8%, 48/69), and keratinization (4.3%, 3/69). Most of the subepithelial pathology was fibrosis (82.6%, 57/69), and inflammation was noted in 17.4% (12/69) of the patients. Subepithelial fibrosis was the most common pathological feature in patients exhibiting stenosis with a squamous epithelium, while inflammation was more strongly correlated with patients with a columnar epithelium. However, there was no correlation between the histopathological findings and treatment outcomes. CONCLUSION: Our histopathological findings suggest that primary fibrosis of the stenotic punctum was caused by intrinsic inflammation of the puncta rather than spreading from the conjunctiva or eyelid. Punctoplasty was effective in treating punctal stenosis, regardless of the epithelial type.


Assuntos
Dacriocistorinostomia/métodos , Doenças do Aparelho Lacrimal/diagnóstico , Aparelho Lacrimal/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Feminino , Seguimentos , Humanos , Doenças do Aparelho Lacrimal/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Microscopia com Lâmpada de Fenda , Tomografia de Coerência Óptica , Resultado do Tratamento
10.
Stem Cell Res Ther ; 10(1): 246, 2019 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-31399042

RESUMO

BACKGROUND: Graves' ophthalmopathy (GO) is a complication of Graves' disease (GD), in which orbital connective tissues become inflamed and increase in volume and orbital fibroblasts within the orbital fat and extraocular muscles differentiate into adipocytes in vitro when stimulated by hormones, several cytokines, and growth factors including TSH, IGF-1, IL-1, interferon γ, and platelet-derived growth factor. Human placental mesenchymal stem cells (hPMSCs) have immunomodulatory effects in disease pathogenesis. Although a number of studies have reported that hPMSCs can elicit therapeutic effects, these are not sufficient. Therefore, we constructed a GO animal model in order to find out the hPMSCs recovery effect. METHODS: We investigated their anti-adipogenic effects in in vitro cultures of orbital fibroblasts established from GO patients. Primary orbital fibroblasts were exposed to differentiation medium for 10 days. After being co-cultured with hPMSCs, the characteristics of orbital fibroblast were determined by Oil Red O stain and real-time PCR. Then, we explored the in vivo regulatory effects of hPMSCs in an experimental mouse model of GO. We developed the GO mouse model using immunization by leg muscle electroporation of pTriEx1.1Neo-hTSHR A-subunit plasmid. Human PMSC injection was performed into the left orbit. We also analyzed the effects of hPMSCs in the GO animal model. RESULT: We found that hPMSCs inhibited a lipid accumulation and activated factors, such as ADIPONECTIN, PPARγ, C/EBPα, and TGFß2 genes in adipogenesis-induced primary orbital fibroblasts from GO patients. Moreover, hPMSCs were highly effective at ameliorating adipogenesis in the orbital tissue of the model. CONCLUSION: These data indicate that hPMSCs recover pathogenic activation of orbital fibroblasts in animals undergoing experimental GO and confirm the feasibility of applying hPMSCs as a novel treatment for GO patients.


Assuntos
Adipogenia , Diferenciação Celular , Oftalmopatia de Graves/patologia , Células-Tronco Mesenquimais/metabolismo , Placenta/citologia , Adiponectina/metabolismo , Animais , Células Cultivadas , Citocinas/sangue , Modelos Animais de Doenças , Feminino , Fibroblastos/citologia , Fibroblastos/metabolismo , Humanos , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Camundongos , Camundongos Endogâmicos BALB C , Órbita/citologia , Órbita/patologia , PPAR gama/metabolismo , Gravidez , Glândula Tireoide/patologia
11.
Korean J Ophthalmol ; 33(1): 1-7, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30746906

RESUMO

PURPOSE: To understand the ophthalmic clinical features and outcomes of facial nerve palsy patients who were referred to an ophthalmic clinic for various conditions like Bell's palsy, trauma, and brain tumor. METHODS: A retrospective study was conducted of 34 eyes from 31 facial nerve palsy patients who visited a clinic between August 2007 and July 2017. The clinical signs, management, and prognosis were analyzed. RESULTS: The average disease period was 51.1 ± 20.6 months, and the average follow-up duration was 24.0 ± 37.5 months. The causes of facial palsy were as follows: Bell's palsy, 13 cases; trauma, six cases; brain tumor, five cases; and cerebrovascular disease, four cases. The clinical signs were as follows: lagophthalmos, 24 eyes; corneal epithelial defect, 20 eyes; conjunctival injection, 19 eyes; ptosis, 15 eyes; and tearing, 12 eyes. Paralytic strabismus was found in seven eyes of patients with another cranial nerve palsy (including the third, fifth, or sixth cranial nerve). Conservative treatments (like ophthalmic ointment or eyelid taping) were conducted along with invasive procedures (like levator resection, tarsorrhaphy, or botulinum neurotoxin type A injection) in 17 eyes (50.0%). Over 60% of the patients with symptomatic improvement were treated using invasive treatment. At the time of last following, signs had improved in 70.8% of patients with lagophthalmos, 90% with corneal epithelium defect, 58.3% with tearing, and 72.7% with ptosis. The rate of improvement for all signs was high in patients suffering from facial nerve palsy without combined cranial nerve palsy. CONCLUSIONS: The ophthalmic clinical features of facial nerve palsy were mainly corneal lesion and eyelid malposition, and their clinical course improved after invasive procedures. When palsy of the third, fifth, or sixty cranial nerve was involved, the prognosis and ophthalmic signs were worse than in cases of simple facial palsy. Understanding these differences will help the ophthalmologist take care of patients with facial nerve palsy.


Assuntos
Blefaroptose/etiologia , Tratamento Conservador/métodos , Gerenciamento Clínico , Paralisia Facial/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Blefaroptose/diagnóstico , Blefaroptose/terapia , Criança , Pré-Escolar , Progressão da Doença , Paralisia Facial/fisiopatologia , Feminino , Seguimentos , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Adulto Jovem
12.
Graefes Arch Clin Exp Ophthalmol ; 257(4): 821-826, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30796562

RESUMO

PURPOSE: This study aims to investigate the surgical outcomes of a novel epiblepharon correction method based on the pathologic features of epicanthal tissue. The correlation between the pathology and clinical presentations was also studied. METHODS: This retrospective study included 72 eyelids of 36 children with epiblepharon and epicanthal folds. From July 2013 to March 2016, epicanthal tension-releasing procedure of subdermal fibrinolysis with orbicularis oculi ring myotomy were performed in 36 children. Photographs before and after operation were analyzed with Image J program. A clinical severity of the epiblepharon was scored based on the lower eyelid skin fold height (mild to severe). Subdermal fibrosis index was defined as the portion of fibrosis in low power field (× 40) and eyelid contour was assessed with custom software (MATLAB). Eighty eyelids without eyelid pathology were analyzed to establish the normal eyelid contour. The epicanthal tissues were classified into three categories: mild, moderate, and severe fibrosis. RESULTS: The mean age of the patients was 5.5 years. Intercanthal distance (ICD) ratio was defined as Inner ICD (IICD)/outer ICD (OICD). The IICD/OICD was 0.41 in the severe epiblepharon group that is significantly longer compared to that of the mild epiblepharon group (0.38). Subdermal fibrosis index was higher in severe epiblepharon group. Eyelid contour was normalized and the cilia touch was resolved after the epicanthal tension-releasing procedure. CONCLUSION: Epicanthal tension-releasing procedure with orbicularis oculi ring myotomy achieved favorable surgical outcomes. Clinical correlations with pathologic findings and satisfactory results of the procedure suggest that medial epicanthal fibrosis is the main pathologic feature causing epiblepharon and epicanthal folds.


Assuntos
Doenças Palpebrais/congênito , Pálpebras/anormalidades , Pálpebras/patologia , Músculos Faciais/cirurgia , Músculos Oculomotores/cirurgia , Procedimentos Cirúrgicos Oftalmológicos , Adolescente , Grupo com Ancestrais do Continente Asiático/etnologia , Criança , Pré-Escolar , Doenças Palpebrais/etnologia , Doenças Palpebrais/cirurgia , Pálpebras/cirurgia , Feminino , Humanos , Masculino , República da Coreia/epidemiologia , Estudos Retrospectivos
13.
Korean J Ophthalmol ; 32(6): 445-450, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30549467

RESUMO

PURPOSE: To compare the tear film lipid layer thickness (LLT) between patients with incomplete nasolacrimal duct obstruction (NLDO) and normal controls and to analyze the changes in tear film LLT and blinking pattern after silicone tube intubation in NLDO patients. METHODS: We reviewed the medical records of 68 eyes in 52 incomplete NLDO patients who underwent silicone tube intubation from January 2017 to July 2017. The LLT, blinking pattern, and Meibomian gland image were measured with the LipiView II ocular surface interferometer. The Meibomian gland drop-out ratio was measured using the polygon selection tool in the Image J program. Tear meniscus height, which is the other lacrimal indicator, was assessed with spectral-domain optical coherence tomography. RESULTS: Tear meniscus height was significantly decreased after silicone tube intubation (p < 0.01). Preoperative minimum, maximum, and average LLT values were 62.4 ± 24.0, 86.7 ± 17.9, and 71.7 ± 23.3 nm, respectively. Significant changes in the minimum, maximum, and average LLT (74.8 ± 23.6, 98.8 ± 11.0, and 91.6 ± 16.1 nm, respectively) were observed after silicone tube intubation (p < 0.001, p = 0.001, and p < 0.001). The partial blinking/total blinking ratio in 20 seconds and the Meibomian gland drop-out ratio showed no significant change after silicone tube intubation. CONCLUSIONS: Overall, the LLT was increased after silicone tube intubation. Silicone tube intubation may be helpful in maintaining LLT with a normalized of amount of tears.


Assuntos
Interferometria , Intubação/instrumentação , Obstrução dos Ductos Lacrimais/terapia , Metabolismo dos Lipídeos/fisiologia , Silicones , Lágrimas/metabolismo , Idoso , Piscadela/fisiologia , Feminino , Humanos , Obstrução dos Ductos Lacrimais/metabolismo , Luz , Masculino , Pessoa de Meia-Idade , Ducto Nasolacrimal/metabolismo , Estudos Retrospectivos
14.
Korean J Ophthalmol ; 32(5): 344-352, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30311456

RESUMO

PURPOSE: The lower eyelid serves important roles in tear distribution and drainage. The purpose of this study was to measure the tear meniscus height (TMH) with anterior segment optical coherence tomography after lower blepharoplasty. METHODS: A total of 52 eyes from 26 patients treated between July 2012 and June 2015 were included in the study. A transcutaneous or transconjunctival approach was performed, depending on whether (1) the supportive lower lid orbicularis oculi muscle was tightened, (2) the middle lamella was elongated, (3) minimal fat was removed or transpositioned, and (4) lateral canthal support was established. Marginal reflex distance 2 and marginal nose distance were analyzed with Image J software. TMH was measured with anterior segment optical coherence tomography. A paired t-test and Wilcoxon signed-rank test were used for statistical comparisons. RESULTS: Marginal reflex distance 2 decreased and marginal nose distance increased with both surgical techniques. TMH decreased from 337.3 ± 117.9 to 289.3 ± 69.1 µm (p = 0.024) in patients who had transcutaneous lower blepharoplasty, but increased from 186.5 ± 35.5 to 274.8 ± 58.3 µm (p = 0.000) in patients who had transconjunctival lower blepharoplasty. Medial and lateral TMHs decreased significantly from 228.8 ± 80.7 to 152.7 ± 42.1 µm (p = 0.008) in patients with transcutaneous lower blepharoplasty. TMH was significantly restored after lower blepharoplasty with either approach. CONCLUSIONS: Enhancing the lower eyelid position combined with orbicularis muscle tightening and lateral canthal support can normalize the TMH following lower eyelid blepharoplasty.


Assuntos
Blefaroplastia/métodos , Blefaroptose/cirurgia , Pálpebras/diagnóstico por imagem , Lágrimas/química , Tomografia de Coerência Óptica/métodos , Blefaroptose/diagnóstico , Blefaroptose/metabolismo , Pálpebras/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Estudos Retrospectivos
15.
Stem Cells Int ; 2018: 3932615, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30210548

RESUMO

Adipose tissue contains abundant multipotent mesenchymal stem cells with strong proliferative and differentiating potential into adipocytes, osteocytes, and chondrocytes. However, adipose-derived mesenchymal stem cells (ASCs) showed variable characteristics based on the tissue-harvesting site. This study aimed at comparing human adipose-derived mesenchymal stem cell from the orbit (Orbital ASCs) and abdomen (Abdominal ASCs). Orbital and abdominal ASCs were isolated during an upper or lower blepharoplasty operation and liposuction, respectively. Flow cytometric analysis was done to analyze the surface antigens of ASCs, and cytokine profiles were measured using Luminex assay kit. The multilineage potential of both ASCs was investigated using Oil Red O, alizarin red, and alcian staining. Reverse transcriptase polymerase chain reaction (RT-PCR) was performed to measure mRNA levels of genes involved in these trilineage differentiations. Our results showed that both types of ASCs expressed the cell surface markers which are commonly expressed stem cells; however, orbital-ASCs showed higher expressions of CD73, CD90, CD105, and CD146 than abdominal ASCs. Unlikely, orbital-ASC expressed CD31, CD45 and HLA-DR lesser than abdominal-ASCs. Orbital ASCs secreted higher concentrations of eotaxin, fractalkine, IP-10, GRO, MCP-1, IL-6, IL-8, and RANTES but lower MIP-1α, FGF-2, and VEGF concentrations than abdominal-ASCs. Our result showed that orbital ASCs have higher potential towards adipogenic and osteogenic differentiation but lower tendency to chondrogenesis when compared with abdominal ASCs. In conclusion, tissue-harvesting site is a strong determinant for characterization of adipose-derived mesenchymal stem cells. Understanding defining phenotypes of such cells is useful for making suitable choices in different regenerative clinical indications.

16.
Korean J Ophthalmol ; 32(1): 1-7, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29376224

RESUMO

PURPOSE: In the present study, we investigated the treatment efficacy and clinical outcomes of botulinum neurotoxin-A (BoNT-A) administered for longer than 5 years to patients with essential blepharospasm. METHODS: We retrospectively reviewed 19 patients (male : female = 8 : 11) diagnosed with essential blepharospasm between March 2006 and July 2016 who underwent BoNT-A injections for over 5 years and were followed. Efficacy of 297 injections of Botox (n = 162), Meditoxin (n = 75), Hugel-tox (n = 40), or Dysport (n = 20) was based on the symptom improvement score at the final injection (-1, worse; 0, same; 1, better). Injection dose (botox unit), duration of efficacy (months), and adverse events were also investigated. RESULTS: Based on product type, significant differences in patient age (59.3 ± 9.8 years), disease period (5.0 ± 5.4 years), number of botulinum neurotoxin injections before visiting our clinic (1.6 ± 2.6), and follow-up period (7.2 ± 1.6 years) were not observed. Treatment efficacy score and injection dose of repetitive injections were 0.1 ± 0.5 and 39.1 ± 4.0 units, respectively, and did not show significant differences with repeated injections. Duration of response was 5.9 ± 5.4 months, but this significantly decreased as the injections were repeated (p < 0.01). Among the 297 injections, adverse events occurred 12 times (4.0%) with no severe sequelae. CONCLUSIONS: In this study, we showed that repetitive, long-term BoNT-A injections are considered a stable and effective treatment for essential blepharospasm in terms of consistent injection dose and maintenance of treatment efficacy. However, the duration of long-term efficacy could be decreased in patients injected repetitively.


Assuntos
Blefarospasmo/tratamento farmacológico , Toxinas Botulínicas Tipo A/uso terapêutico , Fármacos Neuromusculares/uso terapêutico , Adulto , Idoso , Blefarospasmo/fisiopatologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
17.
J Tissue Eng Regen Med ; 12(3): e1441-e1449, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28857477

RESUMO

Different damage factors are known to trigger cell death in the optic nerves. Use of mesenchymal stem cells is a possible treatments option for traumatic optic nerve injury due to their ability to secrete protective cytokines and recovery factors. In this study, we investigated the neuroprotective effects of human placenta-derived mesenchymal stem cells (hPMSCs) using an established optic nerve compression model and model of R28 cells that were exposed to hypoxia. Forty percent of axon death was seen in induced in vivo optic nerve injury model (p < .05), and 70% of R28 cells exposed to cobalt chloride (CoCl2 ), leading to hypoxia, underwent apoptosis (p < .05). After intravenous injection of hPMSCs into tail vein, there was 25% improvement of axon survival in vivo (p < .05). R28 cells incubated with hPMSCs after exposure to hypoxic condition resulted in 50% increased cell survival compared with R28 cells without hPMSC exposure (p < .05), suggesting the active release of multiple factors related to cell survival. In addition, we found that Nf-κb protein mediates neuroprotection pathway via up-regulation of target proteins regulated by hPMSCs. Therefore, we assert that Nf-κb was one of the mediator proteins in a recovery pathway induced by hPMSCs. In conclusion, these indicate that transactivation of Nf-κb protein has a critical role in recovery mechanism by hPMSCs. We suggest that hPMSCs have abilities to recover neuronal damages by up-regulating the expression of genes associated with axon survival and can a better understanding of the possible role of hPMSCs in the treatment modalities of optic nerve injury.


Assuntos
Axônios/fisiologia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , NF-kappa B/metabolismo , Síndromes de Compressão Nervosa/terapia , Nervo Óptico/patologia , Placenta/citologia , Transdução de Sinais , Animais , Apoptose , Linhagem Celular , Sobrevivência Celular , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Síndromes de Compressão Nervosa/patologia , Regeneração Nervosa , Gravidez , Ratos Sprague-Dawley
18.
Stem Cells Int ; 2017: 4206187, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28894469

RESUMO

Ex vivo culture of human limbal epithelial cells (LECs) is used to treat limbal stem cell (LSC) deficiency, a vision loss condition, and suitable culture systems using feeder cells or serum without animal elements have been developed. This study evaluated the use of human umbilical cord or placenta mesenchymal stem cells (C-MSCs or P-MSCs, resp.) as feeder cells in an animal/serum-free coculture system with human LECs. C-/P-MSCs stimulated LEC colony formation of the stem cell markers (p63, ABCG2) and secreted known LEC clonal growth factors (keratinocyte growth factor, ß-nerve growth factor). Transforming growth factor-ß-induced protein (TGFBIp), an extracellular matrix (ECM) protein, was produced by C-/P-MSCs and resulted in an increase in p63+ ABCG2+ LEC colonies. TGFBIp-activated integrin signaling molecules (FAK, Src, and ERK) were expressed in LECs, and TGFBIp-induced LEC proliferation was effectively blocked by a FAK inhibitor. In conclusion, C-/P-MSCs enhanced LEC culture by increasing growth of the LSC population by secreting growth factors and the ECM protein TGFBIp, which is suggested to be a novel factor for promoting the growth of LECs in culture. C-/P-MSCs may be useful for the generation of animal-free culture systems for the treatment of LSC deficiency.

19.
Acta Ophthalmol ; 95(7): e619-e624, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28029231

RESUMO

PURPOSE: Anterior segment optical coherence tomography (AS-OCT) was used to image the lacrimal punctum and establish normal punctal parameters including the tear volume inside the punctum. METHODS: This study included totally 67 eyes from 38 normal subjects. Punctal parameters and tear meniscus height (TMH) were measured using spectralis OCT anterior-segment scans. Outer punctal diameter (OPD), punctal depth, tear well diameter (TWD), tear well depth, punctal reserve (PR) and lower eyelid TMH were assessed. Authors defined a 'tear well' as a pool of standing tears in the punctum. Punctal reserve was defined as the difference between punctal depth and tear well depth. RESULTS: Outer punctal diameter was 614.6 ± 195.6 µm, the punctal depth was 545.8 ± 270.1 µm, TWD was 229.9 ± 133.8 µm, the tear well depth was 434.9 ± 247.8 µm, the PR was 110.9 ± 72.9 µm, the PR ratio was 0.20 ± 0.17, and the TMH was 222.9 ± 88.8 µm. The punctal depth decreased significantly according to the patient's age (correlation coefficient = -0.352, respectively). CONCLUSION: AS-OCT is useful for improving anatomical understanding of the lacrimal punctal structure. Quantitative punctum and tear well measurements were correlated with TMH.


Assuntos
Aparelho Lacrimal/anatomia & histologia , Lágrimas/metabolismo , Tomografia de Coerência Óptica/métodos , Estudos Transversais , Feminino , Voluntários Saudáveis , Humanos , Aparelho Lacrimal/metabolismo , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
20.
Mol Med Rep ; 14(3): 2276-82, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27430300

RESUMO

The pathogenesis of Graves' ophthalmopathy (GO) remains to be entirely elucidated. The present study aimed to determine the association between phenotypic expression of the MTHFR gene and susceptibility to GO in patients with Graves' disease (GD). A prospective case­controlled study was conducted with 122 patients with GD and GO (n=72) or without GO (n=50) and 100 healthy controls in South Korea. Patient history, including smoking, nutritional status, thyroid function and antithyroid antibodies were investigated and clinical activity score, VISA classification (which includes vision, inflammation, strabismus and appearance/exposure) and orbit computed tomography were evaluated. Fasting plasma total homocysteine (tHcy) concentration was measured, and genotype analysis of the MTHFR gene was conducted. The TT homozygous genotype was associated with a two­fold increased risk of GO [adjusted odds ratio (AOR), 2.19; 95% confidence interval (CI), 0.78­6.14]. However, this result was not significant. The TT genotype significantly increased the risk of GO compared with that in healthy controls (AOR, 2.92; 95% CI, 1.11­7.65). The MTHFR 677CT/1298AA genotype decreased the risk of GO in patients with GD (AOR, 0.26; 95% CI, 0.08­0.91). tHcy levels in patients with GD without GO were significantly higher than in patients with GO, however, they were within the normal limit. The current study identified an association between MTHFR polymorphisms and GO. These results will aid understanding of the pathogenesis of GO and facilitate development of genetic therapeutic strategies.


Assuntos
Estudos de Associação Genética , Predisposição Genética para Doença , Oftalmopatia de Graves/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Polimorfismo de Nucleotídeo Único , Adulto , Alelos , Biomarcadores , Estudos de Casos e Controles , Feminino , Genótipo , Oftalmopatia de Graves/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , República da Coreia
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