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1.
Ophthalmologe ; 118(5): 439-448, 2021 May.
Artigo em Alemão | MEDLINE | ID: mdl-33730306

RESUMO

BACKGROUND: In recent years, many experimental and clinical studies have shown that in glaucoma, neuronal degeneration occurs not only at the level of the retina and optic nerve, but also along the entire visual pathway and the brain. OBJECTIVE: This article presents the neuroprotective effects of citicoline and their mechanisms in glaucoma disease. MATERIALS AND METHODS: The relevance of citicoline is explained against the background of neuroanatomy, neuroimaging, and the pathogenesis of glaucoma. Data from experimental and clinical studies are presented and a conclusion is drawn for clinical application. RESULTS: Citicoline has a neuroprotective effect via mechanisms relevant to glaucoma. The neuroprotective effect of citicoline in open-angle glaucoma can be demonstrated functionally and morphologically. It is independent of the glaucoma damage and intraocular pressure, and usually occurs only after 1 year. The effects of oral citicoline occur at a daily dose of 500-1000 mg. Citicoline can be taken permanently or in cycles. No side effects occurred in the studies when taking citicoline. Citicoline can improve cognitive performance and thus treatment adherence as well as quality of life in glaucoma patients. CONCLUSION: This relatively old nootropic drug, which is now marketed as a food supplement, seems to be a valuable addition to conventional treatment and also a rational option for prophylaxis of open-angle glaucoma.


Assuntos
Glaucoma , Fármacos Neuroprotetores , Citidina Difosfato Colina/uso terapêutico , Glaucoma/tratamento farmacológico , Humanos , Pressão Intraocular , Fármacos Neuroprotetores/uso terapêutico , Qualidade de Vida , Tonometria Ocular
2.
Biosci Rep ; 40(10)2020 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-33026069

RESUMO

PURPOSE: Confocal laser scanning microscopy (CLSM) is a non-invasive technique for cellular in vivo imaging of the human cornea. CLSM screening was evaluated for early detection of corneal nerve morphology changes and neuropathogenic events in different stage multiple myeloma (MM) patients. As MM patients show disease as well as therapy-related neuropathological symptoms, CLSM potentially provides a tool for non-invasive early detection of neuropathogenic events. CLSM findings were compared with the severity of peripheral neuropathic (PNP) symptoms. METHODS: The study enrolled 25 MM patients in which bilateral ophthalmologic examination was performed including unilateral CLSM. Further peripheral nerve function was clinically evaluated using the conventional neuropathy symptom and neuropathy deficit scores (NDSs). RESULTS: In 18/25 MM patients, CLSM detected atypical morphological appearance of bulb-like enlarged nerve endings in the corneal sub-basal nerve plexus. These neuromas were only found in patients showing moderate to severe PNP, in patients with mild or lacking PNP neuromas were absent. CONCLUSIONS: CLSM provides a novel non-invasive diagnostic tool for identification of neuromas in cancer patients affected by therapy or disease-related neuropathologies, perspectival allowing early neuronal degenerative process detection and monitoring.


Assuntos
Córnea/inervação , Microscopia Confocal , Mieloma Múltiplo/patologia , Nervo Óptico/patologia , Neurite Óptica/patologia , Papiledema/patologia , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/complicações , Neurite Óptica/etiologia , Papiledema/etiologia , Valor Preditivo dos Testes
3.
R Soc Open Sci ; 7(9): 200441, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33047019

RESUMO

To elucidate and to inhibit post-surgical fibrotic processes after trabeculectomy in glaucoma therapy, we measured gene expression in a fibrotic cell culture model, based on transforming growth factor TGF-ß induction in primary human tenon fibroblasts (hTFs), and used Connectivity Map (CMap) data for drug repositioning. We found that specific molecular mechanisms behind fibrosis are the upregulation of actins, the downregulation of CD34, and the upregulation of inflammatory cytokines such as IL6, IL11 and BMP6. The macrolide antibiotic Josamycin (JM) reverses these molecular mechanisms according to data from the CMap, and we thus tested JM as an inhibitor of fibrosis. JM was first tested for its toxic effects on hTFs, where it showed no influence on cell viability, but inhibited hTF proliferation in a concentration-dependent manner. We then demonstrated that JM suppresses the synthesis of extracellular matrix (ECM) components. In hTFs stimulated with TGF-ß1, JM specifically inhibited α-smooth muslce actin expression, suggesting that it inhibits the transformation of fibroblasts into fibrotic myofibroblasts. In addition, a decrease of components of the ECM such as fibronectin, which is involved in in vivo scarring, was observed. We conclude that JM may be a promising candidate for the treatment of fibrosis after glaucoma filtration surgery or drainage device implantation in vivo.

4.
BMC Ophthalmol ; 19(1): 118, 2019 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-31126280

RESUMO

BACKGROUND: To examine morphological and functional results after pars plana vitrectomy (PPV) with sulfur hexafluoride (SF6) gas tamponade due to macula-on and macula-off rhegmatogenous retinal detachment (RRD) during 6 months of the follow-up. METHODS: The study included 62 eyes that underwent successful PPV with SF6 tamponade with macula-on (34 eyes) and macula-off (28 eyes) RRD preoperatively. The best-corrected visual acuity (BCVA), Amsler test, M-charts, optical coherence tomography (OCT) and microperimetry were performed at 1, 3 and 6 months postoperatively. RESULTS: Results of the Amsler test were abnormal postoperatively in 54% of the patients in the group with macula-off and in 32% of the patients with macula-on RRD. Horizontal M-charts improved significantly from 0.33 to 0.2, vertical M-charts- from 0.29 to 0.17 during 6 months of the follow-up. There was a significant increase in the central retinal thickness (CRT) and average thickness (AT) between follow-up examinations only in the macula-off group. 29 of 62 eyes (47%) after surgery (equally with macula-on and macula-off RRD) showed morphological changes in OCT in the macular region, as epiretinal membrane, macular edema, subretinal fluid or alterations of the outer layers of the retina. The average threshold in microperimetry increased significantly within both groups during the follow-up. CONCLUSION: Both horizontal and vertical M-charts scores, as were as microperimetry sensitivity improved significantly during the 6 months of the follow-up both in macula-on and macula-off group. Although PPV with SF6 gas tamponade was successful, almost half of eyes revealed anatomical changes in the macular region in OCT both with macula-on and macula-off group. TRIAL REGISTRATION: Current Controlled Trials NCT03902795 registered on 03/04/2019. Retrospectively registered.


Assuntos
Tamponamento Interno/métodos , Macula Lutea/patologia , Descolamento Retiniano/cirurgia , Vitrectomia/métodos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Descolamento Retiniano/patologia , Descolamento Retiniano/fisiopatologia , Estudos Retrospectivos , Hexafluoreto de Enxofre/administração & dosagem , Tomografia de Coerência Óptica/métodos , Transtornos da Visão/fisiopatologia , Acuidade Visual/fisiologia
5.
Biosci Rep ; 39(5)2019 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-30967499

RESUMO

We aimed to identify differences in cytokine/chemokine levels in the aqueous humor (AH) of primary open-angle glaucoma (POAG) patients who suffered from scarring, compared with POAG patients with no scarring after trabeculectomy surgery. Identification of differently expressed cytokines and chemokines may help to understand scarring and fibrotic processes following trabeculectomy, and to make predictions for the outcome of fistulating surgery in the future. Furthermore, the identification of cell signaling pathways involved in fibrosis offers the opportunity for a more specific antifibrotic therapy with reduced side effects, and an improvement in long-term surgical outcome.Eight samples of AH were collected during trabeculectomy surgery and commercially available cytokine/chemokine arrays were used. Specific, differently expressed proteins (cytokines/chemokines) in AH samples from patients with positive and negative surgery outcomes were detected. These proteins were classified based on their known profibrotic, inflammatory, adhesive, and apoptotic properties. Transforming growth factor ß (TGF-ß) and vascular endothelial growth factor (VEGF) were among the most important profibrotic cytokines that we detected. Differences in the fold change of protein expression were highly significant between patients after successful and failed trabeculectomy surgery, and these were processed and visualized using ExprEssence software.This pilot study revealed differences in concentrations of cytokines/chemokines in AH between the two examined groups of patients. Our findings suggest that a positive outcome from trabeculectomy is strongly related to an inhibition of the fibrosis process.


Assuntos
Quimiocinas/genética , Citocinas/genética , Glaucoma de Ângulo Aberto/cirurgia , Trabeculectomia/efeitos adversos , Adolescente , Adulto , Idoso , Humor Aquoso/metabolismo , Criança , Feminino , Glaucoma de Ângulo Aberto/genética , Glaucoma de Ângulo Aberto/metabolismo , Glaucoma de Ângulo Aberto/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Fator de Crescimento Transformador beta/genética , Fator A de Crescimento do Endotélio Vascular/genética
6.
J Trace Elem Med Biol ; 50: 67-72, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30262318

RESUMO

PURPOSE: Selenium supplementation was seen to be linked to glaucoma disease in a previous study (Lillico A. JE, Reid M et al. (2002) Selenium Supplementation and Risk of Glaucoma in the NPC trial University of Arizona, Tucson, AZ., Arizona Cancer Center). As aqueous humor levels of selenium seemed to be associated with primary open-angle glaucoma (POAG), the aim of this study was to analyze concentrations of selenium in aqueous humor samples of patients with POAG and pseudoexfoliation glaucoma (PEXG) in comparison to normal samples. PATIENTS AND METHODS: Thirty-eight aqueous humor samples from patients undergoing cataract surgery were collected: Eleven patients with PEXG (age 65.8 ±â€¯10.69, female 6, male 5), 12 patients with POAG (age 65.3 ±â€¯10.50, female 7, male 5) and 15 patients without glaucoma (age 70.9 ±â€¯12.83, female 10, male 5, controls). Aqueous humor levels of selenium were measured by Flow-Injection-Inductively-Coupled-Plasma-DRC-Mass-Spectrometry (ICP-DRC-MS). RESULTS: Maximum likelihood estimation of the least squares means (LS-means) and the relative 95% confidence limits of selenium aqueous humor levels were 6.90 ±â€¯1.03 µg/L (control), 6.74 ±â€¯1.14 µg/L (POAG) and 8.25 ±â€¯1.18 µg/L (PEXG). The data were modeled using a generalized linear model (GLM) analysis, where selenium was set as dependent variable. The model was corrected for group differences in age and gender. The data show no differences among all the calculated differences between the least square means (LS means), taking in consideration the simultaneous 95% confidence limit and the multiple comparison tests with Tukey-Cramer adjustment. The evaluation of the model disclosed that POAG and PEXG patients had no significantly different aqueous humor selenium concentrations compared to controls and to each other. However, the quantile regression analysis of selenium aqueous humor levels showed differences in quantiles for open-angle glaucoma patients considering age and gender. CONCLUSION: As no significant difference in aqueous humor concentration of selenium was detected between open-angle glaucoma and controls, however, quantile analysis showed differences in quantiles levels for different age ranges in open-angle glaucoma patients, the trace element selenium seemed to be linked to glaucoma disease, yet not in a major role.


Assuntos
Humor Aquoso/química , Glaucoma de Ângulo Aberto/metabolismo , Selênio/análise , Idoso , Feminino , Humanos , Análise dos Mínimos Quadrados , Funções Verossimilhança , Masculino , Espectrometria de Massas , Pessoa de Meia-Idade , Oligoelementos/análise
7.
J Ophthalmol ; 2018: 5985702, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29750122

RESUMO

PURPOSE: To analyse visual field (VF) defects obtained using semiautomated kinetic perimetry (SKP) in patients suffering from Leber hereditary optic neuropathy (LHON). METHODS: Twenty-two eyes of eleven consecutive LHON male patients with confirmed mitochondrial 11778G>A DNA mutation were prospectively examined with the V4e stimulus of SKP in both eyes. The mean time after the onset of LHON was one year. The area of obtained isopters was measured in square degrees (deg2). Additionally, static automated perimetry (SAP) within 30° was performed. RESULTS: Visual acuity ranged from counting fingers to 50 cm to 0.4. VFs obtained with SKP showed central scotomas in 18 eyes (82%); the periphery of the VF in these eyes remained intact. The mean area of central scotoma was 408.8 deg2, and the mean area of the peripheral VF was 12291.1 deg2; SAP also revealed central scotoma in these patients. In four eyes (18%) with the worst visual acuity, only the residual central island of VF was found using SKP (mean area 898.4 deg2). SAP was difficult to obtain in these patients. CONCLUSIONS: SKP provides additional clinical information in regard to the visual function of LHON patients. SKP enables the quantification of the area of central scotoma, preserved peripheral VF, and residual central island of vision. Using V4 stimulus is especially useful in LHON patients with poor visual acuity, when SAP is difficult to obtain.

8.
Int J Mol Sci ; 19(5)2018 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-29747422

RESUMO

In the cornea, healing of the wounded avascular surface is an intricate process comprising the involvement of epithelial, stromal and neuronal cell interactions. These interactions result to the release of various growth factors that play prominent roles during corneal wound healing response. Bone morphogenetic proteins (BMPs) are unique multi-functional potent growth factors of the transforming growth factor-beta (TGF-β) superfamily. Treatment of corneal epithelial cells with substance P and nerve growth factor resulted to an increase in the expression of BMP7 mRNA. Since BMP7 is known to modulate the process of corneal wound healing, in this present study, we investigated the influence of exogenous rhBMP7 on human corneal epithelial cell and stromal cell (SFs) function. To obtain a high-fidelity expression profiling of activated biomarkers and pathways, transcriptome-wide gene-level expression profiling of epithelial cells in the presence of BMP7 was performed. Gene ontology analysis shows BMP7 stimulation activated TGF-β signaling and cell cycle pathways, whereas biological processes related to cell cycle, microtubule and intermediate filament cytoskeleton organization were significantly impacted in corneal epithelial cells. Scratch wound healing assay showed increased motility and migration of BMP7 treated epithelial cells. BMP7 stimulation studies show activation of MAPK cascade proteins in epithelial cells and SFs. Similarly, a difference in the expression of claudin, Zink finger E-box-binding homeobox 1 was observed along with phosphorylation levels of cofilin in epithelial cells. Stimulation of SFs with BMP7 activated them with increased expression of α-smooth muscle actin. In addition, an elevated phosphorylation of epidermal growth factor receptor following BMP7 stimulation was also observed both in corneal epithelial cells and SFs. Based on our transcriptome analysis data on epithelial cells and the results obtained in SFs, we conclude that BMP7 contributes to epithelial-to-mesenchymal transition-like responses and plays a role equivalent to TGF-β in the course of corneal wound healing.


Assuntos
Proteína Morfogenética Óssea 7/metabolismo , Substância Própria/citologia , Células Epiteliais/metabolismo , Proteína Morfogenética Óssea 7/genética , Linhagem Celular Transformada , Movimento Celular/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Receptores ErbB/metabolismo , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Perfilação da Expressão Gênica , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Fator de Crescimento Neural/farmacologia , Fosforilação/efeitos dos fármacos , Fosfotirosina/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Proteínas Recombinantes/farmacologia , Reprodutibilidade dos Testes , Substância P/farmacologia , Telomerase/metabolismo , Transcriptoma/genética , Cicatrização/efeitos dos fármacos
9.
Curr Eye Res ; 43(5): 611-620, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29400577

RESUMO

Purpose/Aim of the study: The corneal and conjunctival epithelium interact with each other and reciprocally modulate the levels of soluble mediators to maintain balance in the ocular surface. The aim of the present study was to analyze paracrine interactions between the corneal and conjunctival epithelium in an inflamed microenvironment (LPS or PMA induction) to test the levels of pro- and anti-inflammatory cytokines and nitric oxide released by the epithelia. MATERIALS AND METHODS: The corneal (pRSV-T) and conjunctival (HC0597) epithelial cell cultures and their indirect co-cultures were treated for 2 h with LPS (E. coli) or for 30 min with phorbol 12-myristate-13-acetate (PMA) to induce inflammation. Cytokine expression (IL-1ß, IL-6, IL-10) and the level of apoptosis were analyzed by ELISA, and the nitric oxide (NO) level by Griess reaction. Cells were incubated for 24 h. RESULTS: The apoptosis of the corneal and conjunctival epithelia decreased (by 43% and 53%, respectively) in co-cultures compared to corresponding monocultures. The conjunctival epithelium produced lower amounts (23%) of NO than the corneal epithelium. PMA and LPS had comparable effects on the levels of NO in mono- and co-cultures. The levels of the tested cytokines changed depending on the type of cell culture and culture conditions (mono- vs. co-cultures and inflammation). The most striking changes were observed for IL-6 expression. CONCLUSIONS: Paracrine interactions between the corneal and conjunctival epithelia may regulate microenvironmental homeostasis during artificially induced inflammation among others by balancing the levels of NO, cytokines, and the viability of cells.


Assuntos
Comunicação Celular/fisiologia , Microambiente Celular/fisiologia , Túnica Conjuntiva/metabolismo , Células Epiteliais/metabolismo , Epitélio Corneano/metabolismo , Ceratite/metabolismo , Comunicação Parácrina/fisiologia , Apoptose , Células Cultivadas , Técnicas de Cocultura , Citocinas/metabolismo , Ensaio de Imunoadsorção Enzimática , Homeostase/fisiologia , Humanos , Ceratite/induzido quimicamente , Lipopolissacarídeos/farmacologia , Óxido Nítrico/metabolismo , Acetato de Tetradecanoilforbol/farmacologia
10.
Int J Mol Sci ; 19(2)2018 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-29401709

RESUMO

Following injury, corneal stromal keratocytes transform into repair-phenotype of activated stromal fibroblasts (SFs) and participate in wound repair. Simultaneously, ongoing bi-directional communications between corneal stromal-epithelial cells also play a vital role in mediating the process of wound healing. Factors produced by stromal cells are known to induce proliferation, differentiation, and motility of corneal epithelial cells, which are also subsequently the main processes that occur during wound healing. In this context, the present study aims to investigate the effect of SFs conditioned medium (SFCM) on corneal epithelial cell function along with substance P (SP). Antibody microarrays were employed to profile differentially expressed cell surface markers and cytokines in the presence of SFCM and SP. Antibody microarray data revealed enhanced expression of the ITGB1 in corneal epithelial cells following stimulation with SP whereas SFCM induced abundant expression of IL-8, ITGB1, PD1L1, PECA1, IL-15, BDNF, ICAM1, CD8A, CD44 and NTF4. All these proteins have either direct or indirect roles in epithelial cell growth, movement and adhesion related signaling cascades during tissue regeneration. We also observed activation of MAPK signaling pathway along with increased expression of focal adhesion kinase (FAK), paxillin, vimentin, ß-catenin and vasodilator-stimulated phosphoprotein (VASP) phosphorylation. Additionally, epithelial-to-mesenchymal transition (EMT) regulating transcription factors Slug and ZEB1 expression were enhanced in the presence of SFCM. SP enriched the expression of integrin subunits α4, α5, αV, ß1 and ß3 whereas SFCM increased α4, α5, αV, ß1 and ß5 integrin subunits. We also observed increased expression of Serpin E1 following SP and SFCM treatment. Wound healing scratch assay revealed enhanced migration of epithelial cells following the addition of SFCM. Taken together, we conclude that SFCM-mediated sustained activation of ZEB1, Slug in combination with upregulated migration-associated integrins and ERK (Extracellular signal-regulated kinase)-FAK-paxillin axis, may lead to induce type 2 EMT-like changes during corneal epithelial wound healing.


Assuntos
Meios de Cultivo Condicionados/farmacologia , Células Epiteliais/efeitos dos fármacos , Fibroblastos/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Células Estromais/metabolismo , Cicatrização/efeitos dos fármacos , Anticorpos , Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/metabolismo , Linhagem Celular , Córnea/efeitos dos fármacos , Córnea/metabolismo , Córnea/patologia , Lesões da Córnea/metabolismo , Lesões da Córnea/patologia , Lesões da Córnea/reabilitação , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Fibroblastos/patologia , Quinase 1 de Adesão Focal/genética , Quinase 1 de Adesão Focal/metabolismo , Humanos , Integrina beta1/genética , Integrina beta1/metabolismo , Proteínas dos Microfilamentos/genética , Proteínas dos Microfilamentos/metabolismo , Proteína Quinase 1 Ativada por Mitógeno/genética , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Modelos Biológicos , Paxilina/genética , Paxilina/metabolismo , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Cultura Primária de Células , Análise Serial de Proteínas , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Transdução de Sinais , Fatores de Transcrição da Família Snail/genética , Fatores de Transcrição da Família Snail/metabolismo , Células Estromais/patologia , Substância P/farmacologia , Vimentina/genética , Vimentina/metabolismo , Cicatrização/genética , Homeobox 1 de Ligação a E-box em Dedo de Zinco/genética , Homeobox 1 de Ligação a E-box em Dedo de Zinco/metabolismo , beta Catenina/genética , beta Catenina/metabolismo
11.
Exp Eye Res ; 170: 8-12, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29448041

RESUMO

PURPOSE: Ocular autonomic control is mediated by sympathetic and parasympathetic nerve fibres. Their interactions are complemented by primary afferent nerve fibers of and intrinsic choroidal neurons (ICN). As the vasodilatative neuropeptide, vasoactive intestinal peptide (VIP), is expressed in extrinsic and intrinsic ocular neurons, it is of special interest in ophthalmic research. Since circadian changes of ocular blood flow are known in humans and birds, this study aimed at investigating VIP expression at different daytimes in chicken choroid, the preferred model species in ICN research. METHODS: 12 eyes of 12 chickens were retrieved, slaughtered at 8.00-9.30 a.m. (n = 6) and 8.00 p.m. (n = 6), respectively, and choroidal wholemounts were prepared for immunofluorescence of VIP. VIP-positive ICN of both groups were quantified and density of VIP-positive axons assessed semi-quantitatively. In 28 additional eyes retrieved in the morning (n = 14) and evening (n = 14), choroidal VIP content was determined by ELISA. Morning and evening data were analyzed statistically. NADPH-diaphorase (NADPH-d, ICN cell marker) was done at additional 12 whole mount choroids of 12 chicken, retrieved in the morning (n = 6) and evening (n = 6). RESULTS: (1) Numbers of VIP positive neurons differed significantly between morning: (239.17 ±â€¯113.9) and evening: (550.83 ±â€¯245.7; p = 0.018). (2) Numbers of VIP-positive perikarya were significantly more accumulated in the temporal part of the choroid in the evening than in the morning (p = 0.026). (3) VIP positive axon density was found to be similar throughout the choroid in the morning and evening. (4) Number of NADPH-d positive neurons was not significantly different between morning (848.8 ±â€¯399.5) and evening (945.8 ±â€¯622.1, p > 0.05). (5) ELISA demonstrated a significant difference of VIP content (p = 0.012) in tissues harvested in the morning (145.41 ±â€¯43.3 pg/ml) compared to evening (221.44 ±â€¯106.3 pg/ml). CONCLUSIONS: As VIP positive axon density was similar in the morning and the evening throughout the choroid, PPG and ICN seemed to contribute equally to the axon network. Yet, changes in the total choroidal VIP content, the numbers of VIP positive perikarya, reflecting the intracellular VIP content, and their topographical distribution at two different days-times argue for a different status of activation of both neuronal sources in contrast to the equal amount of NADPHD-d positive neurons. The higher VIP content in the evening, compared to the morning, correlates with a known circadian rhythm of a lower IOP and a higher choroidal thickness at night. Thus, these changes may argue for a potential role of ICN in the regulation of ocular homeostasis and integrity.


Assuntos
Corioide/inervação , Neurônios/metabolismo , Fotoperíodo , Peptídeo Intestinal Vasoativo/metabolismo , Animais , Biomarcadores/metabolismo , Contagem de Células , Galinhas , Ritmo Circadiano/fisiologia , Ensaio de Imunoadsorção Enzimática , Técnica Indireta de Fluorescência para Anticorpo , Modelos Animais , NADPH Desidrogenase/metabolismo
12.
J Trace Elem Med Biol ; 45: 150-155, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29173472

RESUMO

PURPOSE: Trace elements might play a role in the complex multifactorial pathogenesis of open-angle glaucoma. The aim of this study was to analyze concentrations of trace elements in aqueous humor samples of patients with primary open-angle glaucoma (POAG) and pseudoexfoliation glaucoma (PEXG). PATIENTS AND METHODS: Thirty-three aqueous humor samples were obtained from patients undergoing cataract surgery: 12 patients with POAG (age 65.3±10.50, female 8, male 4), 10 patients with PEXG (age 65.9±11.27, female 6, male 4) and 11 patients without glaucoma (age 69.5±13.70, female 7, male 4) serving as controls. Aqueous humor levels of cadmium, iron, manganese, cobalt, copper and zinc were measured by Flow-Injection-Inductively-Coupled-Plasma-Mass-Spectrometry (FI-ICP-MS). RESULTS: From the statistical evaluation, we observed that patients with POAG had significantly higher aqueous humor levels of zinc (p=0.006) compared to controls. Increased aqueous humor levels of zinc were also observed in patients with PEXG in relation to control (p=0.0006). For iron we observed a significantly reduction in PEXG compared to control (p=0.002) and a significant difference between POAG and PEXG (p=0.0091). No significant differences were observed in aqueous humor levels of manganese, cobalt, copper, cadmium between glaucoma and control patients. No differences were seen for iron (POAG vs. controls). Analysis of trace element ratios was added. CONCLUSION: Significant differences in aqueous humor levels of zinc and iron between glaucoma and control patients support the hypothesis that these trace elements are involved in the pathogenesis of open-angle glaucoma.


Assuntos
Humor Aquoso/metabolismo , Glaucoma de Ângulo Aberto/metabolismo , Oligoelementos/metabolismo , Idoso , Cádmio/metabolismo , Cobalto/metabolismo , Cobre/metabolismo , Feminino , Humanos , Masculino , Manganês/metabolismo , Pessoa de Meia-Idade
13.
J Ophthalmol ; 2017: 8109390, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28840039

RESUMO

AIM: To report outcomes of pars plana vitrectomy (PPV) in pediatric retinal detachment (RD) with proliferative vitreoretinopathy (PVR), complications, factors influencing the final anatomical and functional results. METHODS: Retrospective consecutive case series of 14 eyes. Average postoperative follow-up period was 34 months. RESULTS: Mean age of patients was 10 years; eleven patients (79%) were males. The most common etiology was trauma (57%), the second-myopia (36%) and one case of uveitis (7%). At the day of presentation, the best-corrected visual acuity (BCVA) was worse than hand motion (50%); macula was detached in 86% of cases. Simultaneous PPV and phacoemulsification with intraocular lens (IOL) implantation were performed in 12 cases (86%). The most common endotamponade during PPV was silicone oil (93%). Anatomic reattachment was accomplished in 86% of cases. Final BCVA was equal or better than 0.1 in 50% of patients. The postoperative complications were found in 5 eyes (36%). CONCLUSION: Complete PPV was allowed for anatomically reattached retina and preserved vision in pediatric complex RD with PVR. However, visual outcomes were not satisfactory. Preserving vision in children with RD is of great importance for their future motor and intellectual development. This trial is registered with ClinicalTrials.gov Identifier: NCT03208205.

14.
Pharmacol Rep ; 69(4): 722-729, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28551532

RESUMO

BACKGROUND: Tryptophan metabolites formed along kynurenine pathway may affect cell proliferation and tissue function. This pathway presents potential sites for drug discovery. Tryptophan and its metabolites kynurenine and kynurenic acid may be involved in the physiology and pathology of the ocular surface. The purpose of this work is to investigate the effect exerted by tryptophan, kynurenine and kynurenic acid upon corneal epithelium. METHODS: A SkinEthic™ HCE human reconstructed corneal epithelium model was used. WST-1 test was used to examine cell proliferation and viability, and the Griess reaction for nitric oxide determination. The levels of IL-6 and IL-10 were measured by means of ELISA assay. All analyses were carried out after the cells were exposed to tryptophan, kynurenine and kynurenic acid at concentrations of 5, 50 or 100µM for 0-24h and 24-48h. RESULTS: Tryptophan (100µM), kynurenine (100µM) and kynurenic acid (5-100µM) slightly increased the viability and proliferation of corneal epithelium. All of the tested compounds decreased cellular NO release. Kynurenine (50-100µM) and tryptophan (50-100µM) decreased while tryptophan (5µM) and kynurenic acid (100µM) increased the release of IL-6. All of the tested substances increased the level of IL-10 and decreased the IL-6 to IL-10 ratio. CONCLUSIONS: Tryptophan, kynurenine and kynurenic acid affect physiological processes in corneal epithelium and therefore may play a significant role in the physiology and pathology of the ocular surface. Our results indicate that the use of these compounds may be considered in the treatment of ocular surface diseases.


Assuntos
Epitélio Corneano/efeitos dos fármacos , Ácido Cinurênico/farmacologia , Cinurenina/farmacologia , Triptofano/farmacologia , Antidepressivos de Segunda Geração/farmacologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/fisiologia , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Interleucina-10/genética , Interleucina-10/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Óxido Nítrico , Técnicas de Cultura de Tecidos
15.
J Ophthalmol ; 2017: 6232151, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28553550

RESUMO

Purpose. To evaluate visual and safety outcomes of 23-gauge (G) pars plana vitrectomy (PPV) with application of perfluorocarbon liquid (PFCL) for intraoperative protection of the macula during intraocular foreign body (IOFB) removal. Methods. Retrospective study of 42 patients who underwent 23 G PPV for IOFB removal from posterior segment with intraoperative PFCL application for the macula shielding. Collected data included corrected distance visual acuity (CDVA), size of IOFB, and complication rate. The mean follow-up period was 12 months. Results. The mean preoperative CDVA was 0.54 logMAR (SD 0.46), and the final mean CDVA was 0.68 logMAR (SD 0.66). All IOFBs were metallic with mean dimensions of 4.6 mm × 2.1 mm. Twenty-two IOFBs were removed through the corneal tunnel and 20 IOFBs through the sclerotomy. No intraoperative iatrogenic lesion of the macula was observed. As a tamponade, silicon oil was applied in 31 eyes, SF6 gas in 5 eyes, air in 4 eyes, and 2 eyes required no tamponade. Secondary retinal detachment was observed in 17% of cases, but at the end of the follow-up, all the retinas were attached. Conclusion. PFCL application during PPV is a safe method of protecting the macula from unexpected falling of the metallic IOFB during its removal.

16.
J Ophthalmol ; 2017: 5084319, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28163930

RESUMO

Purpose. To evaluate functional and anatomical results of pars plana vitrectomy (PPV) in the retinal detachment (RD) followed by severe eye trauma. Methods. Retrospective analysis of medical records of forty-one consecutive patients treated with 23-gauge PPV due to traumatic RD. Age, gender, timing of PPV, visual acuity, and presence of intraocular foreign body (IOFB) and proliferative vitreoretinopathy (PVR) were included in the analysis. Results. Mean age of patients was 47 years; the majority of patients were men (88%). Closed globe injury was present in 21 eyes and open globe injury in 20 eyes (IOFB in 13 eyes, penetration injury in 4 eyes, and eye rupture in 3 eyes). Mean follow-up period was 14 months; mean timing of PPV was 67 days. Twenty-seven (66%) eyes had a functional success; 32 eyes (78%) had anatomical success. As a tamponade silicone oil was used in 33 cases and SF6 gas in 8 cases. Conclusions. Severe eye injuries are potentially devastating for vision, but vitreoretinal surgery can improve anatomical and functional outcomes. Among analysed pre- and intra- and postoperative factors, absence of PVR, postoperative retinal attachment, and silicone oil as a tamponade were related to significantly improved visual acuity.

17.
BMC Infect Dis ; 16: 496, 2016 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-27647122

RESUMO

BACKGROUND: Endophthalmitis is potentially devastating intraocular inflammation following eye trauma or surgery. We describe the visual outcomes and causative pathogens in acute bacterial postoperative and posttraumatic endophthalmitis treated with immediate pars plana vitrectomy (PPV) with Vancomycin dissolved in the infusion fluid. METHODS: Clinical records of consecutive 30 patients with postoperative endophthalmitis and 15 patients with posttraumatic endophthalmitis were evaluated. Vancomycin was administered constantly in the infusion fluid at the time of complete PPV. Cultures were prepared from anterior chamber paracentesis. The mean follow-up period was 13 months. RESULTS: The visual acuities were improved in 38 cases (84 %) and remained stable in seven cases (16 %). Median post-PPV visual acuity was 1.0 logMAR in a group with postoperative endophthalmitis and 1.3 logMAR in a group with posttraumatic endophthalmitis (p < 0.05). Twenty cases (44 %) were culture-positive (Staphylococcus, Streptococcus, Enterococcus and Bacillus spp). CONCLUSIONS: Early PPV with Vanomycin in infusion leads to vision improvement in patients with both posttraumatic and postoperative endophthalmitis. In our series of 45 cases culture was positive only in half of the cases.


Assuntos
Antibacterianos/uso terapêutico , Endoftalmite/cirurgia , Infecções Oculares Bacterianas/tratamento farmacológico , Complicações Pós-Operatórias/tratamento farmacológico , Vancomicina/uso terapêutico , Vitrectomia , Adulto , Idoso , Idoso de 80 Anos ou mais , Endoftalmite/etiologia , Endoftalmite/microbiologia , Infecções Oculares Bacterianas/etiologia , Infecções Oculares Bacterianas/microbiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Staphylococcus , Streptococcus , Acuidade Visual , Adulto Jovem
18.
J Ophthalmol ; 2016: 7013709, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27642519

RESUMO

Purpose. To evaluate the indications, refraction, and visual and safety outcomes of iris-claw intraocular lens implanted retropupillary with sutureless technique during primary or secondary operation. Methods. Retrospective study of case series. The Haigis formula was used to calculate intraocular lens power. In all cases the wound was closed without suturing. Results. The study comprised 47 eyes. The mean follow-up time was 15.9 months (SD 12.2). The mean preoperative CDVA was 0.25 (SD 0.21). The final mean CDVA was 0.46 (SD 0.27). No hypotony or need for wound suturing was observed postoperatively. Mean postoperative refractive error was -0.27 Dsph (-3.87 Dsph to +2.85 Dsph; median 0.0, SD 1.28). The mean postoperative astigmatism was -1.82 Dcyl (min -0.25, max -5.5; median -1.25, SD 1.07). Postoperative complications were observed in 10 eyes. The most common complication was ovalization of the iris, which was observed in 8 eyes. The mean operation time was 35.9 min (min 11 min, max 79 min; median 34, SD 15.4). Conclusion. Retropupilary iris-claw intraocular lens (IOL) implantation with sutureless wound closing is an easy and fast method, ensuring good refractive outcome and a low risk of complication. The Haigis formula proved to be predictable in postoperative refraction.

19.
BMC Ophthalmol ; 16(1): 50, 2016 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-27145831

RESUMO

BACKGROUND: Several techniques for fixation of the posterior chamber intraocular lens (IOL) have been developed. We evaluate long-term functional outcomes and safety of posterior chamber IOL implantation using Hoffman scleral haptic fixation and sutureless Sharioth technique in patients with posttraumatic and postoperative aphakia. METHODS: This retrospective case-series included 42 eyes operated by one surgeon. The data including demographic data, ocular history, preoperative, early postoperative and final best corrected visual acuity (BCVA), rate of complications as well as postoperative IOL position were collected. The mean follow-up was 14.5 months. Hoffman haptic scleral fixation was performed in 31 eyes, Sharioth technique-in 11 eyes. Aphakia was due to eye trauma (19) or complicated cataract surgery (23). RESULTS: Overall, the final BCVA improved in 26 eyes, did not change in 5 eyes, and worsened in 11 eyes. No significant differences in BCVA were found between groups operated with Hoffman scleral fixation and Sharioth technique. Postoperatively, we noticed two dislocations of IOL fixated using Sharioth technique and none after Hoffman technique. No severe complications were observed. CONCLUSION: Both transscleral fixation techniques are feasible methods of secondary IOL implantation in posttraumatic and postoperative aphakia. with low incidence of complications, however visual outcomes are diverse.


Assuntos
Afacia/cirurgia , Implante de Lente Intraocular/métodos , Lentes Intraoculares , Esclera/cirurgia , Técnicas de Sutura , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Complicações Intraoperatórias , Implante de Lente Intraocular/efeitos adversos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/cirurgia , Estudos Retrospectivos , Acuidade Visual , Adulto Jovem
20.
Klin Oczna ; 117(1): 5-8, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26349150

RESUMO

BACKGROUND: Open globe injuries complicated with the presence of an intraocular foreign body constitute a vision threatening condition. PURPOSE: To present the results of pars plana vitrectomy in patients with intraocular foreign body. MATERIAL AND METHODS: Medical records of 22 patients were analyzed. Retrospective analysis of data included visual acuity, age, gender and type of injury. RESULTS: All patients were men and the mean age was 37 years. All injuries occurred while working with a hammer. All patients were treated with pars plana vitrectomy combined with intraocular foreign body removal and internal limiting membrane peeling. The visual acuities improved in 9 cases (41%), in 13 cases (59%) the deterioration of visual acuity was observed, no eye was enucleated. In 14 eyes pars plana vitrectomy was combined with lens removal, in 14 eyes silicone oil was used as a tamponade. CONCLUSIONS: Surgical intervention with pars plana vitrectomy combined with intraocular foreign body removal and cataract extraction may preserve severely traumatized eyes and maintain or even improve vision. ocular trauma, vitrectomy, intraocular foreign body.


Assuntos
Corpos Estranhos no Olho/cirurgia , Ferimentos Oculares Penetrantes/cirurgia , Descolamento Retiniano/cirurgia , Vitrectomia/métodos , Adulto , Corpos Estranhos no Olho/complicações , Corpos Estranhos no Olho/diagnóstico , Ferimentos Oculares Penetrantes/complicações , Ferimentos Oculares Penetrantes/diagnóstico , Feminino , Humanos , Implante de Lente Intraocular/métodos , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Descolamento Retiniano/etiologia , Estudos Retrospectivos , Resultado do Tratamento , Acuidade Visual , Adulto Jovem
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