RESUMO
Corneal opacities are a major cause of vision loss worldwide. However, the current therapies are suboptimal to manage the corneal wound healing process. Therefore, there is an obvious need to develop new treatment strategies that are efficient in promoting wound healing in patients with severe corneal disorders. In this study, we investigated and compared the efficacy of adipose-derived mesenchymal stem cells (ADMSCs) and photobiomodulation (PBM) with polychromatic light in the NIR (600-1200 nm) alone and in combination, on corneal opacity, inflammatory response, and tissue architecture in a rat corneal opacity model created by mechanical injury. All animals were divided into four groups randomly following the injury: injury only (no treatment), ADMSCs treatment, PBM treatment and combined (ADMSCs+PBM) treatment (n = 12 eyes per group). At the 10th and 30th day following injury, corneal opacity formation, neovascularization, and corneal thickness were assessed. On the 30th day the harvested corneas were analyzed by transmission electron microscopy (TEM), histological evaluation, immunohistochemical (IHC) staining and real-time polymerase chain reaction (RT-PCR). On day 30, the corneal opacity score, neovascularization grade, and corneal thickness in all treatment groups were significantly lower in comparison with the untreated injured corneas. The TEM imaging and H&E staining together clearly revealed a significant enhancement in corneal regeneration with improved corneal microenvironment and reduced vascularization in the combined administration of PBM and ADMSCs compared to treatment of PBM and ADMSCs alone. In addition, the IHC staining, and RT-PCR analysis supported our hypothesis that combining ADMSCs therapy with PBM alleviated the inflammatory response, and significantly decreased scar formation compared to either ADMSCs or PBM alone during the corneal wound healing.
Assuntos
Opacidade da Córnea , Células-Tronco Mesenquimais , Ratos , Humanos , Animais , Cicatrização , Células-Tronco , Opacidade da Córnea/terapia , CórneaRESUMO
PURPOSE: To design a novel efficacious scAAV-Gusb viral vector for treating Mucopolysaccharidosis Type VII (MPS VII) caused by a mutation in the ß-Glu gene (Gusb allele). METHODS: ß-Glu expression of single-stranded AAV-Gusb (ssAAV-Gusb) and self-complementary AAV (scAAV-Gusb) vectors are tested with cultured murine Gusb fibroblasts. The scAAV-Gusb vector was chosen in further studies to prolong the life span and treat corneal pathology of Gusb mice via intrahepatic injection of neonates and intrastromal injection in adults, respectively. Corneal pathology was studied using HRT2 in vivo confocal microscope and histochemistry in mice corneas. RESULTS: Both ssAAV-Gusb and scAAV-Gusb vectors expressed murine ß-Glu in cultured Gusb fibroblasts. The scAAV-Gusb vector had higher transduction efficiency than the ssAAV-Gusb vector. To prolong the life span of Gusb mice, neonates (3 days old) were administered with scAAV-Gusb virus via intrahepatic injection. The treatment improves the survival rate of Gusb mice, prolonging the median survival rate from 22.5 weeks (untreated) to 50 weeks (treated). Thereafter, we determined the efficacy of the scAAV-Gusb virus in ameliorating corneal cloudiness observed in aged Gusb mice. Both corneal cloudiness and stroma thickness decreased, and there was the presence of ß-Glu enzyme activity in the Gusb corneas receiving scAAV-Gusb virus associated with morphology change of amoeboid stromal cells in untreated to characteristic dendritic keratocytes morphology after 4-12 weeks of scAAV-Gusb virus injection. CONCLUSION: Intrahepatic injection of scAAV-Gusb is efficacious in prolonging the life span of Gusb mice, and intrastromal injection can ameliorate corneal phenotypes. Both strategies can be adapted for treating other MPS.
Assuntos
Dependovirus , Modelos Animais de Doenças , Terapia Genética , Vetores Genéticos , Mucopolissacaridose VII , Animais , Camundongos , Terapia Genética/métodos , Dependovirus/genética , Mucopolissacaridose VII/terapia , Mucopolissacaridose VII/genética , Fibroblastos , Opacidade da Córnea/terapia , Células Cultivadas , Microscopia Confocal , Córnea/patologia , Camundongos Endogâmicos C57BLRESUMO
Granular corneal dystrophy type 2 (GCD2) is an autosomal dominant corneal stromal dystrophy that is caused by p.Arg124His mutation of transforming growth factor ß induced (TGFBI) gene. It is characterized by well demarcated granular shaped opacities in central anterior stroma and as the disease progresses, extrusion of the deposits results in ocular pain due to corneal epithelial erosion. Also, diffuse corneal haze which appears late, causes decrease in visual acuity. The prevalence of GCD2 is high in East Asia including Korea. Homozygous patients show a severe phenotype from an early age, and the heterozygote phenotype varies among patients, depending on several types of compound heterozygous TGFBI mutations. In the initial stage, conservative treatments such as artificial tears, antibiotic eye drops, and bandage contact lenses are used to treat corneal erosion. Different surgical methods are used depending on the depth and extent of the stromal deposits. Phototherapeutic keratectomy removes anterior opacities and is advantageous in terms of its applicability and repeatability. For deeper lesions, deep anterior lamellar keratoplasty can be used as the endothelial layer is not always affected. Recurrence following these treatments are reported within a wide range of rates in different studies due to varying definition of recurrence and follow-up period. In patients who have undergone corneal laser vision-correction surgeries such as photorefractive keratectomy, LASEK, or LASIK including SMILE surgery, corneal opacity exacerbates rapidly with severe deterioration of visual acuity. Further investigations on new treatments of GCD2 are necessary.
Assuntos
Distrofias Hereditárias da Córnea , Opacidade da Córnea , Úlcera da Córnea , Ceratomileuse Assistida por Excimer Laser In Situ , Ceratectomia Fotorrefrativa , Humanos , Distrofias Hereditárias da Córnea/diagnóstico , Distrofias Hereditárias da Córnea/genética , Distrofias Hereditárias da Córnea/terapia , Córnea/patologia , Ceratectomia Fotorrefrativa/métodos , Ceratomileuse Assistida por Excimer Laser In Situ/efeitos adversos , Opacidade da Córnea/diagnóstico , Opacidade da Córnea/etiologia , Opacidade da Córnea/terapia , Úlcera da Córnea/cirurgia , Fator de Crescimento Transformador beta/genéticaRESUMO
Previously we found that inhibitor of differentiation 3 (Id3) gene, a transcriptional repressor, efficiently inhibits corneal keratocyte differentiation to myofibroblasts in vitro. This study evaluated the potential of adeno-associated virus 5 (AAV5)-mediated Id3 gene therapy to treat corneal scarring using an established rabbit in vivo disease model. Corneal scarring/fibrosis in rabbit eyes was induced by alkali trauma, and 24 h thereafter corneas were administered with either balanced salt solution AAV5-naked vector, or AAV5-Id3 vector (n = 6/group) via an optimized reported method. Therapeutic effects of AAV5-Id3 gene therapy on corneal pathology and ocular health were evaluated with clinical, histological, and molecular techniques. Localized AAV5-Id3 gene therapy significantly inhibited corneal fibrosis/haze clinically from 2.7 to 0.7 on the Fantes scale in live animals (AAV5-naked versus AAV5-Id3; p < 0.001). Furthermore, AAV5-Id3 treatment significantly reduced profibrotic gene mRNA levels: α-smooth muscle actin (α-SMA) (2.8-fold; p < 0.001), fibronectin (3.2-fold; p < 0.001), collagen I (0.8-fold; p < 0.001), and collagen III (1.4-fold; p < 0.001), as well as protein levels of α-SMA (23.8%; p < 0.001) and collagens (1.8-fold; p < 0.001). The anti-fibrotic activity of AAV5-Id3 is attributed to reduced myofibroblast formation by disrupting the binding of E-box proteins to the promoter of α-SMA, a transforming growth factor-ß signaling downstream target gene. In conclusion, these results indicate that localized AAV5-Id3 delivery in stroma caused no clinically relevant ocular symptoms or corneal cellular toxicity in the rabbit eyes.
Assuntos
Doenças da Córnea , Lesões da Córnea , Opacidade da Córnea , Actinas/genética , Álcalis , Animais , Cicatriz/patologia , Cicatriz/terapia , Córnea , Doenças da Córnea/genética , Doenças da Córnea/terapia , Lesões da Córnea/patologia , Lesões da Córnea/terapia , Opacidade da Córnea/patologia , Opacidade da Córnea/terapia , Dependovirus , Fibronectinas/genética , Fibrose , Terapia Genética/métodos , RNA Mensageiro , Coelhos , Fatores de Crescimento Transformadores/genéticaRESUMO
PURPOSE: The aim of this study was to characterize the wide phenotypic spectrum of Peters anomaly and to suggest a management algorithm based on disease phenotype. METHODS: The charts of all children diagnosed with Peters anomaly between January 2000 and December 2013 were reviewed retrospectively. Anterior segment color photographs, anterior segment optical coherence tomography, and ultrasound biomicroscopy images were used to phenotype disease severity and to guide management. Disease severity was categorized to Peters anomaly type I and II according to lens involvement. Peters anomaly type I and II were further categorized from mild to severe disease according to the size and location of corneal opacity. Associated systemic findings were also documented. RESULTS: Eighty eyes of 54 patients with Peters anomaly were identified, of which 28 (51.9%) had unilateral disease. Peters anomaly type I was present in 40 patients (57 eyes, 71.2%) and Peters anomaly type II in 14 patients (23 eyes, 28.8%). Nine eyes (11.3%) had phenotypic features that required observation only, 24 eyes (30%) were amenable to pupillary dilation, 43 eyes (53.8%) with large, dense central opacity required penetrating keratoplasty, and 4 eyes (5.0%) had no intervention because of very poor prognostic features. Associated systemic abnormalities occurred frequently in Peters anomaly (n = 20, 37.0%), with congenital heart defect being the most common morbidity (n = 10, 18.5%). CONCLUSIONS: Peters anomaly presents with a variable phenotype ranging from minimal peripheral corneal opacity to extensive iris and lens adhesions with dense central corneal opacity detrimental to vision. Management can be standardized and guided by an algorithm based on phenotypic severity. Systemic abnormalities should be ruled out, regardless of the severity of Peters anomaly.
Assuntos
Segmento Anterior do Olho/anormalidades , Opacidade da Córnea/diagnóstico , Gerenciamento Clínico , Anormalidades do Olho/diagnóstico , Microscopia com Lâmpada de Fenda/métodos , Tomografia de Coerência Óptica/métodos , Acuidade Visual , Opacidade da Córnea/terapia , Anormalidades do Olho/terapia , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Gravidade do Paciente , Fenótipo , Prognóstico , Estudos RetrospectivosRESUMO
The eye has two converging lenses arranged in series: the cornea and the lens. They combine their powers. The image, which is naturally defocused ad infinitum, by crossing them successively, focuses on the retina to be seen clearly. Edema can cause the cornea to lose transparency while the clouding of lens leads to cataract. The loss of transparency of one or both lenses significantly affects the vision. Treating cataracts is a common practice. However, this can lead to the permanent loss of transparency of the cornea. A graft of the latter must then be carried out. How does this sometimes come about?
TITLE: Quand la cataracte conduit à une greffe de la cornée. ABSTRACT: L'Åil possède deux lentilles convergentes disposées en série : la cornée et le cristallin. Elles associent leurs puissances. L'image qui est naturellement défocalisée à l'infini, en les traversant successivement, se focalise sur la rétine pour être vue nette (Figure 1). Un Ådème peut faire perdre sa transparence à la cornée tandis que le cristallin qui s'opacifie constitue la cataracte. La perte de transparence de l'une ou des deux lentilles affecte la vue significativement. Traiter la cataracte est une pratique banale. Cependant, ceci peut conduire à la perte définitive de transparence de la cornée. Il faut alors réaliser une greffe de cette dernière. Comment en vient-on parfois à cela ?
Assuntos
Catarata/terapia , Opacidade da Córnea/terapia , Transplante de Córnea , Catarata/complicações , Catarata/patologia , Edema da Córnea/etiologia , Edema da Córnea/terapia , Opacidade da Córnea/etiologia , Progressão da Doença , HumanosRESUMO
Purpose: Maintenance of a transparent corneal stroma is imperative for proper vision. The corneal stroma is composed of primarily collagen fibrils, small leucine-rich proteoglycans (SLRPs), as well as sparsely distributed cells called keratocytes. The lattice arrangement and spacing of the collagen fibrils that allows for transparency may be disrupted due to genetic mutations and injuries. The purpose of this study is to examine the therapeutic efficacy of human umbilical cord mesenchymal stem/stromal cells (UMSCs) in treating congenital and acquired corneal opacity associated with the loss of collagen V. Methods: Experimental mice, i.e., wild-type, Col5a1f/f and Kera-Cre/Col5a1f/f (Col5a1∆st/∆st , collagen V null in the corneal stroma) mice in a C57BL/6J genetic background, were subjected to a lamellar keratectomy, and treated with or without UMSC (104 cells/cornea) transplantation via an intrastromal injection or a fibrin plug. In vivo Heidelberg retinal tomograph (HRT II) confocal microscopy, second harmonic generated (SHG) confocal microscopy, histology, and immunofluorescence microscopy were used to assess the corneal transparency of the regenerated corneas. Results: Col5a1∆st/∆st mice display a cloudy cornea phenotype that is ameliorated following intrastromal transplantation of UMSCs. Loss of collagen V in Col5a1∆st/∆st corneas augments the formation of cornea scarring following the keratectomy. UMSC transplantation with a fibrin plug improves the healing of injured corneas and regeneration of transparent corneas, as determined with in vivo HRT II confocal microscopy. Second harmonic confocal microscopy revealed the improved collagen fibril lamellar architecture in the UMSC-transplanted cornea in comparison to the control keratectomized corneas. Conclusions: UMSC transplantation was successful in recovering some corneal transparency in injured corneas of wild-type, Col5a1f/f and Col5a1∆st/∆st mice. The production of collagen V by transplanted UMSCs may account for the regeneration of corneal transparency, as exemplified by better collagen fiber organization, as revealed with SHG signals.
Assuntos
Opacidade da Córnea/congênito , Opacidade da Córnea/terapia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Animais , Colágeno Tipo V/metabolismo , Opacidade da Córnea/patologia , Substância Própria/patologia , Colágenos Fibrilares/metabolismo , Humanos , Camundongos Endogâmicos C57BL , Resultado do Tratamento , Cordão Umbilical/citologiaRESUMO
INTRODUCTION: Corneal tattooing is a noninvasive technique which appears relatively well-tolerated in the medium term. We report the cases of 3 patients with a significant change in the color of their tattoos performed over 5 years previously. PATIENTS AND METHODS: Three patients with a history of intracorneal tattooing several years previously were studied because of a significant change from their initial color. Each patient's file was reviewed with analysis of slit lamp photographs, OCT and specular microscopy. RESULTS: All three patients experienced a significant color change in their tattoos between 5 and 6 years after surgery. The color had changed to golden-brown. DISCUSSION: Retrospective analysis of the components of the tattoo ink found the presence of iron in the black pigment. We believe that pigments composed of iron oxide are transformed into golden-brown ferric iron oxide in the presence of oxygen in the aqueous environment. The presence of moderate corneal edema in these three cases of multioperated patients could explain, in these specific cases, the occurrence of oxidation typically not described. CONCLUSION: Corneal tattooing remains a simple and very interesting technique when partial or total absence of iris causes significant photophobia. However, the significant changes in color that we report more than 5 years later suggest omitting iron from the dyes used for the cornea and limiting its use in cases of limited endothelial prognosis. A long-term evaluation of corneal tattoos appears necessary.
Assuntos
Cor , Córnea/patologia , Complicações Pós-Operatórias/patologia , Tatuagem/efeitos adversos , Adulto , Idoso , Aniridia/patologia , Aniridia/terapia , Corantes/efeitos adversos , Opacidade da Córnea/patologia , Opacidade da Córnea/terapia , Feminino , Seguimentos , Humanos , Tinta , Masculino , Pessoa de Meia-Idade , Pigmentação/fisiologia , Estudos Retrospectivos , Fatores de Tempo , Falha de TratamentoRESUMO
Purpose: To compare the therapeutic effects of human derivatives in a mouse alkali burn model. Methods: The right eyes of mice were injured using NaOH. After alkali injury, one of the following agents was topically administered for 7 d: human amniotic membrane (hAM) suspension, human umbilical cord serum (hUCS), and human peripheral blood serum (hPBS), or saline. The epithelial defect areas on days 1, 2, and 3 degrees of opacity on days 2, 3, and 7, and corneal neovascularization (NV) areas on day 7 were evaluated. Histologic examination and mRNA expression levels of tumour necrosis factor (TNF)-α, interleukin (IL)-6, vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-2, MMP-8, and MMP-9 were also evaluated on day 7. Results: The epithelial defect areas in the hUCS group were smaller than those in the control and hPBS groups on day 3 (p < .05, respectively). The epithelial defect areas in the hAM suspension group showed smaller than those in the control and hPBS groups on days 1 and 2 (p < .05, respectively). The degrees of opacity were lower in all treatment groups than that of the saline control group on day 7 (p < .05, respectively). Corneal NV areas were not different among groups on day 7 (p = 0.20). The expression levels of TNF-α, IL-6, MMP-8, and MMP-9 mRNA and the infiltration of the inflammatory cells in all treatment groups were lesser than those in the control group on day 7 (p< .05, respectively). Conclusions: All treatments reduced inflammatory reactions and corneal opacity development. Corneal reepithelialization was faster in the hUCS group.
Assuntos
Âmnio , Queimaduras Químicas/terapia , Neovascularização da Córnea/terapia , Opacidade da Córnea/terapia , Queimaduras Oculares/terapia , Soro , Hidróxido de Sódio/toxicidade , Animais , Queimaduras Químicas/patologia , Córnea/efeitos dos fármacos , Córnea/patologia , Neovascularização da Córnea/patologia , Opacidade da Córnea/patologia , Queimaduras Oculares/induzido quimicamente , Queimaduras Oculares/patologia , Humanos , Masculino , Camundongos Endogâmicos BALB CRESUMO
INTRODUCTION: Corneal tattooing is a noninvasive technique which appears relatively well-tolerated in the medium term. We report the cases of 3 patients with a significant change in the color of their tattoos performed over 5 years previously. PATIENTS AND METHODS: Three patients with a history of intracorneal tattooing several years previously were studied because of a significant change from their initial color. Each patient's file was reviewed with analysis of slit lamp photographs, OCT and specular microscopy. RESULTS: All three patients experienced a significant color change in their tattoos between 5 and 6 years after surgery. The color had changed to golden-brown. DISCUSSION: Retrospective analysis of the components of the tattoo ink found the presence of iron in the black pigment. We believe that pigments composed of iron oxide are transformed into golden-brown ferric iron oxide in the presence of oxygen in the aqueous environment. The presence of moderate corneal edema in these three cases of multioperated patients could explain, in these specific cases, the occurrence of oxidation typically not described. CONCLUSION: Corneal tattooing remains a simple and very interesting technique when partial or total absence of iris causes significant photophobia. However, the significant changes in color that we report more than 5 years later suggest removing iron from the dyes used for the cornea and limiting its use in cases of limited endothelial prognosis. A long-term evaluation of corneal tattoos appears necessary.
Assuntos
Cor , Córnea/patologia , Opacidade da Córnea , Doenças da Íris , Tatuagem , Adulto , Idoso , Opacidade da Córnea/etiologia , Opacidade da Córnea/patologia , Opacidade da Córnea/terapia , Feminino , Seguimentos , Humanos , Iris/lesões , Iris/patologia , Doenças da Íris/patologia , Doenças da Íris/terapia , Masculino , Pessoa de Meia-IdadeRESUMO
Purpose: To evaluate the safety and feasibility of intrastromal injection of human corneal stromal keratocytes (CSKs) and its therapeutic effect on a rodent early corneal opacity model. Methods: Twelve research-grade donor corneas were used in primary culture to generate quiescent CSKs and activated stromal fibroblasts (SFs). Single and repeated intrastromal injections of 2 to 4 × 104 cells to rat normal corneas (n = 52) or corneas with early opacities induced by irregular phototherapeutic keratectomy (n = 16) were performed, followed by weekly examination of corneal response under slit-lamp biomicroscopy and in vivo confocal microscopy with evaluation of haze level and stromal reflectivity, and corneal thickness using anterior segment optical coherence tomography (AS-OCT). Time-lapse tracing of Molday ION-labelled cells was conducted using Spectralis OCT and label intensity was measured. Corneas were collected at time intervals for marker expression by immunofluorescence, cell viability, and apoptosis assays. Results: Injected CSKs showed proper marker expression with negligible SF-related features and inflammation, hence maintaining corneal clarity and stability. The time-dependent loss of injected cells was recovered by repeated injection, achieving an extended expression of human proteoglycans inside rat stroma. In the early corneal opacity model, intrastromal CSK injection reduced stromal reflectivity and thickness, resulting in recovery of corneal clarity, whereas noninjected corneas were thicker and had haze progression. Conclusions: We demonstrated the safety, feasibility, and therapeutic efficacy of intrastromal CSK injection. The cultivated CSKs can be a reliable cell source for potential cell-based therapy for corneal opacities.
Assuntos
Terapia Baseada em Transplante de Células e Tecidos/métodos , Ceratócitos da Córnea/fisiologia , Opacidade da Córnea/terapia , Substância Própria , Modelos Animais de Doenças , Adulto , Animais , Apoptose , Biomarcadores/metabolismo , Sobrevivência Celular , Células Cultivadas , Ceratócitos da Córnea/citologia , Ceratócitos da Córnea/metabolismo , Opacidade da Córnea/metabolismo , Estudos de Viabilidade , Feminino , Técnica Indireta de Fluorescência para Anticorpo , Humanos , Injeções Intraoculares , Masculino , Microscopia Confocal , Ratos , Ratos Sprague-Dawley , Microscopia com Lâmpada de Fenda , Tomografia de Coerência ÓpticaRESUMO
Purpose: We tested the potential of bone morphogenic protein 7 (BMP7) and hepatocyte growth factor (HGF) combination gene therapy to treat preformed corneal fibrosis using established rabbit in vivo and human in vitro models. Methods: Eighteen New Zealand White rabbits were used. Corneal fibrosis was produced by alkali injury. Twenty-four hours after scar formation, cornea received topically either balanced salt solution (BSS; n = 6), polyethylenimine-conjugated gold nanoparticle (PEI2-GNP)-naked plasmid (n = 6) or PEI2-GNP plasmids expressing BMP7 and HGF genes (n = 6). Donor human corneas were used to obtain primary human corneal fibroblasts and myofibroblasts for mechanistic studies. Gene therapy effects on corneal fibrosis and ocular safety were evaluated by slit-lamp microscope, stereo microscopes, quantitative real-time PCR, immunofluorescence, TUNEL, modified MacDonald-Shadduck scoring system, and Draize tests. Results: PEI2-GNP-mediated BMP7+HGF gene therapy significantly decreased corneal fibrosis in live rabbits in vivo (Fantes scale was 0.6 in BMP7+HGF-treated eyes compared to 3.3 in -therapy group; P < 0.001). Corneas that received BMP7+HGF demonstrated significantly reduced mRNA levels of profibrotic genes: α-SMA (3.2-fold; P < 0.01), fibronectin (2.3-fold, P < 0.01), collagen I (2.1-fold, P < 0.01), collagen III (1.6-fold, P < 0.01), and collagen IV (1.9-fold, P < 0.01) compared to the -therapy corneas. Furthermore, BMP7+HGF-treated corneas showed significantly fewer myofibroblasts compared to the -therapy controls (83%; P < 0.001). The PEI2-GNP introduced >104 gene copies per microgram DNA of BMP7 and HGF genes. The recombinant HGF rendered apoptosis in corneal myofibroblasts but not in fibroblasts. Localized topical BMP7+HGF therapy showed no ocular toxicity. Conclusions: Localized topical BMP7+HGF gene therapy treats corneal fibrosis and restores transparency in vivo mitigating excessive healing and rendering selective apoptosis in myofibroblasts.
Assuntos
Apoptose/efeitos dos fármacos , Proteína Morfogenética Óssea 7/genética , Opacidade da Córnea/terapia , Terapia Genética/métodos , Fator de Crescimento de Hepatócito/genética , Miofibroblastos/patologia , Administração Oftálmica , Animais , Córnea/patologia , Opacidade da Córnea/patologia , Modelos Animais de Doenças , Combinação de Medicamentos , Feminino , Fibrose/terapia , Ouro/química , Marcação In Situ das Extremidades Cortadas , Pressão Intraocular , Nanopartículas Metálicas/química , Plasmídeos/genética , Polietilenoimina/química , Coelhos , Reação em Cadeia da Polimerase em Tempo Real , Tonometria OcularRESUMO
The clinical impact of microplasma jets on rabbit eyes infected by Candida albicans has been investigated. Arrays of such jets produce low-temperature plasma micro-columns suitable for ophthalmic therapeutics and fungal infections, in particular, and the technology is capable of being scaled to surface areas of at least 10 cm2. Keratitis was induced in the right central corneas of rabbits, whereas the left eyes served as a normal group. The rabbits were divided into the plasma non-treated group (control) and plasma treatment group. Histologic analyses of both groups showed marked reductions in the thickness, angiogenesis, and opacity of all rabbit corneas following plasma treatment. Indeed, for treatment times beyond 14 days, infected eyes exhibited no significant differences from the normal group. Healing of rabbit eyes infected by Candida albicans apparently proceeds by disrupting corneal epithelial proliferation, and by reducing fibrotic changes in the stroma. This study demonstrates that low-temperature plasma jets are remarkably effective in healing Candida albicans-infected corneas, thereby providing a promising medical treatment option for keratitis.
Assuntos
Neovascularização da Córnea/terapia , Opacidade da Córnea/terapia , Infecções Oculares Fúngicas/terapia , Ceratite/terapia , Gases em Plasma/uso terapêutico , Animais , Candida albicans/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Candida albicans/patogenicidade , Córnea/irrigação sanguínea , Córnea/efeitos dos fármacos , Córnea/microbiologia , Córnea/patologia , Neovascularização da Córnea/microbiologia , Neovascularização da Córnea/patologia , Opacidade da Córnea/microbiologia , Opacidade da Córnea/patologia , Modelos Animais de Doenças , Infecções Oculares Fúngicas/microbiologia , Infecções Oculares Fúngicas/patologia , Ceratite/microbiologia , Ceratite/patologia , Masculino , CoelhosRESUMO
BACKGROUND: De Barsy syndrome is a rare, autosomal recessive syndrome characterized by cutis laxa, progeroid appearance, ophthalmic opacification, skeletal malformations, growth delays, and intellectual disability. AIMS: The aim of this case series is to identify the anesthetic considerations in the clinical management of patients with de Barsy syndrome. METHODS: A retrospective case review from 1968 to 2016 was performed at a single tertiary medical center to identify patients with de Barsy syndrome who underwent anesthesia for diagnostic and surgical procedures. We collected and analyzed the perioperative records and following data: age, sex, American Society of Anesthesiologists physical status, relevant comorbidities, surgical procedures, anesthesia management, and observed complications. RESULTS: Three patients underwent 64 unique anesthetics for a diverse collection of diagnostic and surgical procedures. An array of anesthetics and techniques were successfully used. Observations of the perioperative period found 7 episodes of intraoperative hyperthermia (>38.3°), a single difficult airway requiring fiberoptic bronchoscopic-guided intubation, and repeatedly difficult intravenous access. CONCLUSION: This expanded case series suggests that providers caring for patients with de Barsy syndrome should be aware of potential challenges with airway management, vascular access, and temperature monitoring.
Assuntos
Anestesia , Opacidade da Córnea/terapia , Cútis Laxa/terapia , Deficiência Intelectual/terapia , Anestésicos Inalatórios , Anestésicos Intravenosos , Criança , Feminino , Febre/epidemiologia , Humanos , Complicações Intraoperatórias/epidemiologia , Complicações Intraoperatórias/terapia , Masculino , Estudos RetrospectivosRESUMO
Se describió un caso con anomalía de Peters, defecto congénito de la córnea que aparece de manera generalmente esporádica y de etiología aun incierta. Se hace referencia a sus formas de presentación y a los posibles tratamientos, siendo el pronóstico más sombrío cuando se acompaña de manifestaciones sistémicas. Se explicó cómo se llegó al diagnóstico que es eminentemente clínico, dejando algunas consideraciones finales(AU)
It described a case with anomaly of Peters, congenital defect of the cornea that appears of way generally sporadic and of etiology even uncertain. It does reference to his forms of presentation and to the possible treatments being the darkest prognosis when it accompanies of systemic manifestations. It explained how the diagnostic was reached. It is essentially clinical, letting some final considerations(AU)
Assuntos
Humanos , Recém-Nascido , Córnea/anormalidades , Opacidade da Córnea/terapiaRESUMO
BACKGROUND AIMS: Mesenchymal stromal cells (MSCs) offer tremendous potential for therapeutic applications for inflammatory diseases. However, tissue-derived MSCs, such as bone marrow-derived MSCs (BM-MSCs), have considerable donor variations and limited expandability. It was recently demonstrated that MSCs derived from induced pluripotent stem cells (iPSC-MSCs) have less pro-tumor potential and greater expandability of homogenous cell population. In this study, we investigated the anti-inflammatory effects and mechanism of iPSC-MSCs in a murine model of chemical and mechanical injury to the cornea and compared the effects with those of BM-MSCs. METHODS: To create an injury, ethanol was applied to the corneal surface in mice, and the corneal epithelium was removed with a blade. Immediately after injury, mice received an intravenous injection of (i) iPSC-MSCs, (ii) BM-MSCs or (iii) vehicle. Clinical, histological and molecular assays were performed in the cornea to evaluate inflammation. RESULTS: We found that corneal opacity was significantly reduced by iPSC-MSCs or BM-MSCs. Histological examination revealed that the swelling and inflammatory infiltration in the cornea were markedly decreased in mice treated with iPSC-MSCs or BM-MSCs. Corneal levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and IL-6 were lower in iPSC-MSC- and BM-MSC-treated mice, compared with vehicle-treated controls. In contrast, iPSC-MSCs with a knockdown of the TNF-α stimulating gene (TSG)-6 did not suppress the levels of inflammatory cytokines and failed to reduce corneal opacity. CONCLUSIONS: Together these data demonstrate that iPSC-MSCs exert therapeutic effects in the cornea by reducing inflammation in part through the expression of TSG-6, and the effects are similar to those seen with BM-MSCs.
Assuntos
Lesões da Córnea/terapia , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Mesenquimais/citologia , Animais , Células da Medula Óssea/citologia , Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/metabolismo , Lesões da Córnea/metabolismo , Opacidade da Córnea/patologia , Opacidade da Córnea/terapia , Modelos Animais de Doenças , Células-Tronco Pluripotentes Induzidas/transplante , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Ceratite/patologia , Ceratite/terapia , Transplante de Células-Tronco Mesenquimais , Camundongos Endogâmicos BALB C , Fator de Necrose Tumoral alfa/metabolismoRESUMO
PURPOSE: To report a case of wavelike interface opacities in a patient who underwent Descemet-stripping automated endothelial keratoplasty (DSAEK) and was managed conservatively over the course of 7 years. METHODS: A 65-year-old woman underwent DSAEK for pseudophakic bullous keratopathy. Textural wavelike opacities were noted in the graft-host interface 6 days postoperatively without evidence of anterior segment inflammation. The patient's vision was also initially limited by the presence of cystoid macular edema (CME). Six months postoperatively, CME had resolved but the patient's vision failed to improve better than 20/80 because of the persistent dense interface opacities. The patient refused to undergo graft exchange despite a suboptimal visual result and she therefore was observed over time. RESULTS: The interface opacities started to regress and her visual acuity improved to 20/30 by 9 months postoperatively. The opacities became gradually less prominent over the next few years, and at 7 years postoperatively, her best-corrected vision was 20/25. CONCLUSION: In this case, observation of this post-DSAEK complication rather than surgical intervention resulted in a favorable long-term visual outcome.
Assuntos
Opacidade da Córnea/etiologia , Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior/efeitos adversos , Transtornos da Visão/etiologia , Idoso , Opacidade da Córnea/fisiopatologia , Opacidade da Córnea/terapia , Feminino , Seguimentos , Humanos , Transtornos da Visão/fisiopatologia , Transtornos da Visão/terapia , Acuidade Visual/fisiologiaRESUMO
OBJECTIVE: To describe clinical, in vivo confocal microscopic, histopathologic, and microbiologic features of canine and feline cases of infectious crystalline keratopathy (ICK). ANIMALS STUDIED: Six dogs and two cats with naturally acquired ICK. PROCEDURES: Medical records of dogs and cats with a clinical diagnosis of ICK were reviewed. Signalment, medical history, clinical findings, and diagnostic evaluations were retrieved, including corneal cytology, histopathology, in vivo confocal microscopy, and microbiology results. RESULTS: All animals presented with fine, needle-like, and branching white crystalline anterior stromal opacities emanating from corneal facets or corneal epithelial defects. Mild conjunctival hyperemia and anterior uveitis were frequently present. Concurrent ocular and systemic diseases were common, including keratoconjunctivitis sicca, corneal sequestrum, diabetes mellitus, hyperadrenocorticism, and malignant neoplasia. Bacteria, with minimal or absent leukocytes, were identified by cytology and histopathology. Histopathologically, the crystalline corneal opacities corresponded with dense accumulations of bacteria present in the interlamellar stromal spaces and forming cord-like projections within the stroma. In vivo confocal microscopy demonstrated deposits of reflective crystalline or amorphous structures within the stroma with a paucity of associated inflammatory changes. The most frequently cultured bacteria were alpha-hemolytic Streptococcus and Staphylococcus species. Resolution of clinical lesions was achieved in most cases with long-term medical or surgical therapy; however, the initiation of medical treatment was associated with an acute, dramatic onset of severe keratitis and anterior uveitis in some animals. CONCLUSIONS: Infectious crystalline keratopathy in dogs and cats shares many features with this condition in human patients. Prolonged medical therapy, or surgical intervention, is required for resolution.