Blue-light filtering alters angiogenic signaling in human retinal pigmented epithelial cells culture model

Background: light exposure and more specifically the spectrum of blue light contribute to the oxidative stress in Age-related macular degeneration (AMD). The purpose of the study was to establish whether blue light filtering could modify proangiogenic signaling produced by retinal pigmented epithelial (RPE) cells under different conditions simulating risk factors for AMD. Methods: three experiments were carried out in order to expose ARPE-19 cells to white light for 48 h with and without blue light-blocking filters (BLF) in different conditions. In each experiment one group was exposed to light with no BLF protection, a second group was exposed to light with BLF protection, and a control group was not exposed to light. The ARPE-19 cells used in each experiment prior to light exposure were cultured for 24 h as follows: Experiment 1) Normoxia, Experiment 2) Hypoxia, and Experiment 3) Lutein supplemented media in normoxia. The media of all groups was harvested after light exposure for sandwich ELISA-based assays to quantify 10 pro-angiogenic cytokines. Results: a significant decrease in angiogenin secretion levels and a significant increase in bFGF were observed following light exposure, compared to dark conditions, in both normoxia and hypoxia conditions. With the addition of a blue light-blocking filter in normoxia, a significant increase in angiogenin levels was observed. Although statistical significance was not achieved, blue light filters reduce light-induced secretion of bFGF and VEGF to near normal levels. This trend is also observed when ARPE-19 cells are grown under hypoxic conditions and when pre-treated with lutein prior to exposure to experimental conditions. Conclusions: following light exposure, there is a decrease in angiogenin secretion by ARPE-19 cells, which was abrogated with a blue light - blocking filter. Our findings support the position that blue light filtering affects the secretion of angiogenic factors by retinal pigmented epithelial cells under normoxic, hypoxic, and lutein-pretreated conditions in a similar manner

Visual impairment impact on the quality of life of the elderly population that uses the public health care system from the western countryside of Pernambuco State, Brazil

OBJETIVO: Avaliar o impacto das doenças oculares sobre a qualidade de vida de uma população idosa do sertão de Pernambuco, localizado na região nordeste do Brasil. MÉTODOS: Foram entrevistados 580 indivíduos acima de 59 anos, por meio do questionário de avaliação de qualidade de vida "Visual Functioning Questionnaire" (VFQ). Todos os indivíduos foram submetidos a exame oftalmológico completo. Os resultados das variáveis quantitativas foram expressos por suas médias e desvios- padrão. Os resultados das variáveis qualitativas foram expressos por suas frequências absolutas e relativas. RESULTADOS: A média de idade foi de 70 ± 8,1 anos. Cerca de 86,0% dos entrevistados declararam ser analfabetos ou ter o ensino fundamental incompleto. As principais queixas foram: baixa visual (71,1%) e ardor/prurido (69,0%). A acuidade visual não era normal em 37,4% dos idosos. Por volta de 75,0% dos entrevistados relataram ter saúde regular ou ruim, e 77,0% diziam ter uma visão regular ou ruim. A qualidade de vida foi considerada pior conforme a piora da condição visual do idoso. CONCLUSÃO: O déficit visual representou um impacto negativo sobre a qualidade de vida dos idosos do sertão Pernambucano

Usefulness of Discarded Vitreous Samples from Routine Vitrectomy

Purpose. To describe the histopathological features of vitreous samples obtained after vitrectomy surgery from diabetic and nondiabetic patients. Methods. Vitreous specimens from 137 patients who underwent vitrectomy for different clinical conditions were analysed. All samples were centrifuged and each resulting pellet was fixed and processed as part of routine paraffin section histopathology. The histopathological features were categorized in a semiquantitative fashion. The samples from diabetic and nondiabetic patients were compared. Results. The 125 included patients (58 diabetic, 60% males) were aged 64.2±13.9 years. The presence of hemorrhage, inflammatory cells, and histiocytes was significantly higher in the diabetic group (P<0.001, P=0.028, and P=0.016, resp.), showing more vessels (P<0.001) and ghost vessels (P=0.049). The presence of inflammatory cells was the feature with the highest sensitivity for detecting diabetes mellitus (98%) and also the highest negative predictive value (89%). In the multivariate analysis, three variables emerged as independent significant predictors of diabetes in vitrectomy samples: hemorrhage, endothelial-lined vessels, and age (P<0.001, P<0.001, and P=0.019, resp.). Conclusions. Different histopathological features can be found in vitreous samples from diabetic patients. Analysis of vitrectomy samples may serve as a tool for diabetes management

In vitro characterization and inhibition of the CXCR4/CXCL12 chemokine axis in human uveal melanoma cell lines

<p>Abstract</p> <p>Purpose</p> <p>The CXCR4/CXCL12 chemokine axis may play a critical role in guiding CXCR4+ circulating malignant cells to organ specific locations that actively secrete its ligand CXCL12 (SDF-1) such as bone, brain, liver, and lungs. We sought to characterize the presence of the CXCR4/CXCL12 axis in five uveal melanoma (UM) cell lines in vitro. The ability of TN14003, a synthetic peptide inhibitor that targets the CXCR4 receptor complex, to inhibit this axis was also assessed.</p> <p>Methods</p> <p>Immunocytochemistry was performed against CXCR4 to confirm expression of this chemokine receptor in all five UM cell lines. Flow cytometry was preformed to evaluate CXCR4 cell surface expression on all five UM cell lines. A proliferation assay was also used to test effects TN14003 would have on cellular proliferation. Inhibition of cellular migration by specifically inhibiting the CXCR4/CXCL12 axis with TN14003 was also investigated. The binding efficacy of TN14003 to the CXCR4 receptor was assessed through flow cytometric methods.</p> <p>Results</p> <p>The CXCR4 receptor was present on all five UM cell lines. All five cell lines expressed different relative levels of surface CXCR4. TN14003 did not affect the proliferation of the five cell lines (p > 0.05). All cell lines migrated towards the chemokine CXCL12 at a level greater than the negative control (p < 0.05). All 5 cell lines pre-incubated with TN14003 prevented cellular migration towards chemokine CXCL12 (p < 0.01). TN14003 preferentially binds CXCR4 to native ligand CXCL12.</p> <p>Conclusion</p> <p>Interfering with the CXCR4/CXCL12 axis, using TN14003 was shown to effectively down regulate UM cell migration in vitro. Knowing that UM expresses the CXCR4 receptor, these CXCR4+ cells may be less likely to colonize distant organs that secrete the CXCL12 ligand, if treated with an inhibitor that binds CXCR4. Further studies should be pursued in order to test TN14003 efficacy in vivo.</p

Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection: A case control study

Introduction: The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods: A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results: None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR- 145 correlated with nadir CD4+ T cell count. Discussion: No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection

Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe

Efeito Do Ranibizumabe E Do Amfenac Nas Habilidades Funcionais Em Células De Melanoma Uveal

Objective: To Evaluate The Effects Of Ranibizumab And Amfenac In Human Uveal Melanoma (Um) Cell Lines And To Explore The Ability Of These Compounds To Sensitize Um Cells To Radiation. Methods: The 92.1 Human Um Cell Line Was Cultured; The Cells Were Then Submitted To The Proposed Treatment (Ranibizumab, Amfenac, And A Combination Of Ranibizumab/Amfenac). Proliferation, Migration, And Invasion Assays Of The 92.1 Um Cell Lines Were Assessed After Pretreatment With Ranibizumab (125 "G/Ml) Or Amfenac (150 Nm), Or The Combination Of Both Compounds. In Addition, Proliferation Rates Were Assessed After Treatment With Ranibizumab And Amfenac, And The Cells Were Subsequently Exposed To Various Doses Of Radiation (0 Gy, 4 Gy And 8 Gy). Results: Proliferation Assay " Cells Treated With A Combination Of Ranibizumab And Amfenac Had Lower Proliferation Rates Compared To Controls (P=0.016) And To The Group Treated Only With Ranibizumab (P=0.033). Migration Assay " A Significantly Lower Migration Rate Was Only Observed In ThObjetivo: Avaliar Os Efeitos Do Ranibizumabe Em Associação Com O Amfenac Nas Células De Melanoma Uveal Humano E A Habilidade De Estas Drogas Sensibilizarem As Células De Melanoma Uveal À Irradiação. Métodos: Células De Melanoma Uveal Humano Do Tipo 92.1 Foram Cultivadas. Posteriormente, As Células Foram Submetidas Ao Tratamento Proposto [Ranibizumabe, Amfenac E A Combinação De Ranibizumabe/Amfenac]. Ensaios De Proliferação, Migração E Invasão Com As Células De Melanoma Uveal Do Tipo 92.1 Foram Realizados Após Tratamento Com Ranibizumabe [125 Microg/Ml], Amfenac [150 Nm] E A Combinação De Ambos Os Compostos. Em Seguida, As Taxas De Proliferação Foram Avaliadas Após Tratamento Com Ranibizumabe E Amfenac Com Subsequente Exposição Das Células A Diferentes Doses De Irradiação [0 Gy, 4 Gy E 8 Gy]. Resultados: Ensaio De Proliferação: Células Tratadas Com Ranibizumabe E Amfenac Combinados Apresentaram Menores Taxas De Proliferação Em Comparação Ao Grupo Controle [P=0,016], E Ao Grupo Tratado Apenas Com Ranibizumabe [Dados abertos - Sucupira - Teses e dissertações (2018

Zika virus in Brazil and macular atrophy in a child with microcephaly

Altino Ventura Fdn, Recife, PE, BrazilUniv Fed Sao Paulo, Dept Ophthalmol, Sao Paulo, BrazilHOPE Eye Hosp, Recife, PE, BrazilUniv Fed Sao Paulo, Dept Ophthalmol, Sao Paulo, BrazilWeb of Scienc