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Homocysteine mediates transcriptional changes of the inflammatory pathway signature genes in human retinal pigment epithelial cells

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International Journal of Ophthalmology(English edition) 2017年第5期10卷 696-704页

作者： Mahavir Singh Suresh C Tyagi Department of Physiology University of Louisville School of Medicine Louisville KY 40202 USA

AIM：To test whether homocysteine（Hcy） can influence the transcriptional profile, we hypothesized that Hcy can lead to the induction of proinflammatory molecules in the retinal cells of aging people.METHODS：An unbiased in vitro inflammatory pathway focused study was designed employing retinal pigment epithelial（RPE） cell line, ARPE-19. Cells were cultured in the presence or absence of Hcy to capture target genes＇ expression profile. Three different concentrations of Hcy were added in the culture medium of confluent monolayers. c RNAs were made from the isolated total RNAs and the labeled c RNA probes were hybridized to microarrays specific for human disease pathway inflammatory cytokines, chemokines and their receptor gene micro-array panels as per manufacture＇s recommendations. Two Hcy up-regulated molecules：IL6 and CEBPB were further validated via Western blot analysis. Hcy＇s effect on ARPE-19 cellular morphology and genomic DNA integrity were also evaluated.RESULTS：Gene microarray analyses of RPE cells in response to Hcy treatment revealed alterations in the expressions of several inflammatory gene transcripts such as CCL5, CEBPB, IL13RA2, IL15 RA, IL6, IL8 and CXCL3 that were up-regulated. The transcripts for C3, CCL2, IL11 RA and IL18 genes exhibited down-regulation. The IL6 and CEBPB expressions were subsequently validated at the protein levels. Treatment of the retinal cells with increasing Hcy concentration influenced their density in culture however their morphology and DNA integrity remained unaffected. CONCLUSION：These findings suggest that Hcy can potentially mediate the expression of chemokines,cytokines and interleukins receptors in the retinal cells without having any debilitating effects on their morphology and the genomic DNA integrity.

关键词： chemokine choroidal neovascularization cytokine gene expression hyperhomocysteinemia inflammation macular degeneration retinal remodeling

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Bevacizumab vs ranibizumab for neovascular age-related macular degeneration in Chinese patients

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International Journal of Ophthalmology(English edition) 2013年第2期6卷 169-173页

作者： Jun Li Han Zhang Peng Sun Feng Gu Zhe-Li Liu Department of Ophthalmology the First Affiliated Hospital of China Medical University

AIM: To compare the clinical efficacy of intravitreal injections of bevacizumab and ranibizumab for treating Chinese patients with neovascular age-related macular degeneration (AMD).METHODS: Among 60 Chinese patients with exudative AMD (60 eyes), 28 received intravitreal bevacizumab injections (1.25mg) and 32 received intravitreal ranibizumab injections (0.5mg), once a month for 3 months and were followed for a total of 6 months. Monthly optical coherence tomography (OCT) was used to determine whether the patients received additional treatments during the follow-up. We compared the baseline and 6 -month follow-up values of mean best-corrected visual acuity (BCVA) and central retinal thickness (CRT) in both groups of patients. We also compared the occurrence of adverse events.RESULTS: At the 6-month follow-up, the mean BCVA (logMAR) of the bevacizumab and ranibizumab treatment groups improved from the baseline measurements of 0.72 ±0.23 and 0.73 ±0.22 to 0.47 ±0.14 and 0.45 ±0.20, respectively (P <0.05 for both groups). However, the change was not significantly different between the two groups. As evaluated by OCT, CRT decreased from 366.71 ±34.72μm and 352 ±36.9μm at baseline to 250.86 ± 41.51μm and 243.22 ±41.38μm in the bevacizumab and ranibizumab groups, respectively (P <0.05 for both groups). However, the change was not significantly different between the two groups. There were no severe local adverse reactions or systemic adverse events.CONCLUSION:Intravitreal bevacizumab and ranibizumab have equivalent effects on BCVA and CRT and appeare safe over the short-term.

关键词： age-related macular degeneration choroidal neovascularization bevacizumab (avastin) ranibizumab (lucentis)

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Evaluation of fundus autofluorescence patterns in age-related macular degeneration

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International Journal of Ophthalmology(English edition) 2016年第12期9卷 1779-1784页

作者： Pradeep Venkatesh Pradeep Sagar Rohan Chawla Varun Gogia Rajpal Vohra Yog Raj Sharma Department of Ophthalmology Dr. Rajendra Prasad Centre for Ophthalmic SciencesAll India Institute of Medical Sciences

AIM： To study the various morphological patterns of fundus autofluorescence （FAF） images in patients with age-related macular degeneration （AMD） in Indian population.METHODS： Totally 179 eyes of 104 patients with clinical diagnosis of AMD were recruited into the study. Autofluorescence images were captured using confocal scanning laser ophthalmoscope and the patterns of FAF were classified.RESULTS： Of 179 eyes, 27 （15.08%） were early AMD, 58 （32.41%） were intermediate AMD, 94 eyes （52.51%） were late AMD. Of 94 eyes with late AMD, 79 （84.04%） were neovascular AMD and 15 （15.96%） were central geographic atrophy. In eyes with early and intermediate AMD, 9 patterns of FAF were noted. Six patterns （normal, minimal change, focal increased, patchy increased, linear, reticular） were similar to that in the published classification. Two patterns （lacelike and speckled） described in the published classification were not found. Three new patterns （focal hypo-fluorescence, patchy hypo-fluorescence, mixed focal hypo-fluorescence and hyper-fluorescence） were detected. In eyes with neovascular AMD, 6 morphological patterns of FAF were noted. Two patterns （mixed hypo-fluorescence and hyper-fluorescence, central hypo-fluorescence with hyper-fluorescent rim） were similar to that in published classification. Two patterns （normal, near normal or normal background fluorescence in the centre of hypo-fluorescent area） described in the published classification were not found. Four new patterns （minimal change, hypo-fluorescent patch, central hypo-fluorescence with surrounding reticular, bull’s eye） were recognized. In eye with central geographic atrophy 5 morphological patterns were noted and these were similar to that in published classification.CONCLUSION： Phenotypic differences in the pattern of FAF exist in the study population compared to existing classification systems.

关键词： age-related macular degeneration fundus autofluorescence lipofuscin choroidal neovascularization

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Tachyphylaxis during ranibizumab treatment of exudative age-related macular degeneration

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International Journal of Ophthalmology(English edition) 2015年第4期8卷 846-848页

作者： Sibel Doguizi Sengul Ozdek Selcen Yuksel Department of Ophthalmology Dogubeyazit State Hospital Department of Ophthalmology Faculty of Medicine Gazi University Faculty of Medicine Biostatistics Department Yildirim Beyazit University

Dear Editor,We are intestigators from Turkey primarily studying exudative age-related macular degeneration(AMD).Here we present the results of our retrospective clinical study on tachyphylaxis development during the treatment of exudative AMD with ranibizumab,which,we believe,will form a basis for further prospective studies to predict the drug response in anti-vascular endothelial growth factor

关键词： choroidal neovascularization BEVACIZUMAB BLINDNESS THERAPY

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