MicroRNA-29a May Influence Myopia Development by Regulating Collagen I

The aim of this study was to characterize the regulatory role of microRNA-29a (miR-29a) in myopia, providing support for potential biomarkers and new therapeutic targets of myopia in humans. The miR-29a expression level was detected in the aqueous humor and peripheral blood plasma of 21 high myopic patients and eight cataract control patients using quantitative polymerase chain reaction. iTRAQ analysis of proteomes was conducted to show the regulatory effect of miR-29a on human scleral fibroblasts (SFs) cultured in vitro. We also assessed proliferation, migration, and collagen I synthesis in SF cells, mediated by miR-29a. MiR-29a expression was significantly higher in the aqueous humor of highly myopic patients than in the cataract control patients (fold change: 4.861, p = 0.001). miR-29a inhibited the synthesis of type I collagen in human SF cells and enhanced cell migration, but had no significant effect on cell proliferation. MiR-29a was highly expressed in aqueous humor of myopia patients and inhibited the synthesis of type I collagen in human SF cells in vivo, thereby it may play an important role in myopia development.</p

The literature search process.

<p>Flow diagram depicts the screening process of retrieved articles, including the reason for and number of exclusions. CFH = complement factor H; PCV = polypoidal choroidal vasculopathy.</p

Systematic Review and Meta-Analysis of the Association between Complement Factor H I62V Polymorphism and Risk of Polypoidal Choroidal Vasculopathy in Asian Populations

<div><p>Purpose</p><p>To investigate whether the polymorphism rs800292 (184G>A, I62V) in the complement factor H gene is associated with polypoidal choroidal vasculopathy (PCV) and the genetic difference between PCV and neovascular age-related macular degeneration (nAMD), in Asian populations.</p><p>Methods</p><p>A comprehensive literature search was performed in PubMed, Medline, Web of Science, and reference lists. A system review and meta-analysis of the association between I62V and PCV and/or nAMD were performed from 8 studies involving 5,062 subjects. The following data from individual studies were extracted and analyzed: 1) comparison of I62V polymorphisms between PCV and controls; 2) comparison of I62V polymorphisms between PCV and nAMD. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using fixed-effects models. The Q-statistic test was used to assess heterogeneity, and Egger’s test was used to evaluate publication bias. Sensitivity analysis and cumulative meta-analysis were also performed.</p><p>Results</p><p>The I62V polymorphism showed a significant summary OR₁ for genotype GA+GG versus homozygous genotype AA was 3.18 (95% CI, 2.51–4.04, <i>P</i><<i>0.00001</i>), the OR₂ of heterozygous genotype GA versus AA was 2.29 (95% CI: 1.79–2.94, <i>P</i><<i>0.00001</i>), the OR₃ of homozygous genotype GG versus AA was 4.42 (95% CI: 3.45–5.67, <i>P</i><<i>0.00001</i>), and the OR₄ of allele G versus A was 2.04 (95% CI: 1.85–2.26, <i>P</i><<i>0.00001</i>). Sensitivity analysis indicated the robustness of our findings, and evidence of publication bias was not observed in our meta-analysis. Cumulative meta-analysis revealed that the summary ORs were stable. There was no significant difference in every genetic model between PCV and nAMD (n = 5, OR₁ = 0.92, OR₂ = 0.96, OR₃ = 0.90, OR₄ = 0.94).</p><p>Conclusions</p><p>Our analysis provides evidence that the I62V polymorphism is associated with an increased risk of PCV. The variant of I62V could be a promising genetic biomarker of PCV in Asian populations.</p></div

Forest plots of meta-analysis of the association between I62V polymorphism and PCV.

<p>Odds ratios (black <i>squares)</i> and 95% confidence intervals (bars) are given for each study. Also shown are the <i>diamonds</i> of the summary ORs based on the Mantel–Haenszel fixed-effects model (M-H Overall). CI = confidence interval; OR = odds ratio. A: OR₁(GG+GA vs AA); B: OR₂ (GA vs AA); C: OR₃ (GG vs AA); D: OR₄ (G vs A).</p

Allele and Genotype Distribution of the I62V Polymorphism.

<p>HWE = HardyeWeinberg equilibrium; NA = not available; nAMD = neovascular age-related macular degeneration; PCV = polypoidal choroidal vasculopathy.</p

Cumulative meta-analysis of the association between I62V polymorphism and PCV.

<p>Every circle represents the pooled OR when studies accumulated over time, and the horizontal line represents the 95% confidence interval of pooled OR. A: OR₁(GG+GA vs AA); B: OR₂ (GA vs AA); C: OR₃ (GG vs AA); D: OR₄ (G vs A).</p

Results of Leave-One-Out Sensitivity Analysis.

<p>The horizontal axis shows the omitted study. The horizontal axis represents the odds ratio. Every circle indicates the pooled OR when the left study is omitted in this meta-analysis. The two ends of every broken line represent the respective 95% confidence interval. A: OR₁(GG+GA vs AA); B: OR₂ (GA vs AA); C: OR₃ (GG vs AA); D: OR₄ (G vs A).</p

Meta-analysis compared the allelic frequencies of I62V between PCV and nAMD.

<p>CI = confidence interval; M-H = Mantel–Haenszel model; nAMD = neovascular age-related macular degeneration; OR = odds ratio; PCV = polypoidal choroidal vasculopathy.</p

Main Characteristics of the Studies Included in the Meta-Analysis.

<p>NA = not available; nAMD = neovascular age-related macular degeneration; PCV = polypoidal choroidal vasculopathy.</p><p>*The number of cases or controls was changed in the next meta-analysis, but the reason was not given.</p

DataSheet_2_Salicylic acid delays pear fruit senescence by playing an antagonistic role toward ethylene, auxin, and glucose in regulating the expression of PpEIN3a.docx

Salicylic acid (SA) and ethylene (ET) are crucial fruit senescence hormones. SA inhibited ET biosynthesis. However, the mechanism of SA delaying fruit senescence is less known. ETHYLENE INSENSITIVE 3 (EIN3), a key positive switch in ET perception, functions as a transcriptional activator and binds to the primary ET response element that is present in the promoter of the ETHYLENE RESPONSE FACTOR1 gene. In this study, a gene encoding putative EIN3 protein was cloned from sand pear and designated as PpEIN3a. The deduced PpEIN3a contains a conserved EIN3 domain. The evolutionary analysis results indicated that PpEIN3a belonged to the EIN3 superfamily. Real-time quantitative PCR analysis revealed that the accumulation of PpEIN3a transcripts were detected in all tissues of this pear. Moreover, PpEIN3a expression was regulated during fruit development. Interestingly, the expression of PpEIN3a was downregulated by SA but upregulated by ET, auxin, and glucose. Additionally, the contents of free and conjugated SA were higher than those of the control after SA treatment. While the content of ET and auxin (indole-3-acetic acid, IAA) dramatically decreased after SA treatment compared with control during fruit senescence. The content of glucose increased when fruit were treated by SA for 12 h and then there were no differences between SA treatment and control fruit during the shelf life. SA also delayed the decrease in sand pear (Pyrus pyrifolia Nakai. ‘Whangkeumbae’) fruit firmness. The soluble solid content remained relatively stable between the SA treated and control fruits. This study showed that SA plays an antagonistic role toward ET, auxin, and glucose in regulating the expression of PpEIN3a to delay fruit senescence.</p