PDF(Pubmed)
Abstract：
Background: Age and sex are the most significant risk of factors for advanced Fuchs dystrophy. Nevertheless, few data are available on the hormone\'s receptor pattern expressed in adult and advanced fuchs endothelial corneal dystrophy (FECD). We investigated the impact of gender, growth factors and extracellular matrix (ECM) regulatory proteins expressed by the dystrophic endothelia. Methods: Ten dystrophic endothelial tissues and 10 normal endothelial sheets (corneoscleral specimens; Eye Bank) were used for this characterization study. Hormones\' receptors (ERα, AR, PR, SHBG), few growth factors (VEGFA, βNGF, TGFβ1), some ECM regulators (MMP1, MMP7) and few inflammatory cytokines (IFNγ, IL10) were analyzed by real-time RT-PCR. Results: ERα transcripts were significantly increased, AR and SHBG transcripts were decreased in Fuchs endothelia from female patients, and no changes were detected for PR transcripts. VEGFA, βNGF and TGFβ1 transcripts were upregulated in Fuchs\' endothelia, but not significantly linked to gender. High MMP1 and low MMP7 transcripts\' expression were detected in Fuchs\' specimens, mainly in males than females. An increased IFNγ (Th1) transcript expression was observed in females than males, and a trend to increase for IL10 (Th2) transcripts was detected in males than females. Conclusions: Our findings clearly indicate that hormone receptors, growth factors and matrix mediators as well as a Th1 pathway are predominant in Fuchs\' dystrophy, displaying a pattern of expression specific for the female phenotype. The differential expression of hormones\' receptors and the Th1/Th2 ratio might prompt to new theories to be tested in vitro and in vivo models, such as the use of hormonal substitute for counteracting this endothelial cell lost.
摘要：
背景：年龄和性别是晚期Fuchs营养不良的最重要危险因素。然而，关于成人和晚期fuchs内皮角膜营养不良（FECD）中表达的激素受体模式的数据很少。我们调查了性别的影响，由营养不良性内皮表达的生长因子和细胞外基质（ECM）调节蛋白。方法：使用10个营养不良的内皮组织和10个正常的内皮片（角膜巩膜标本；眼库）进行这项表征研究。激素受体(ERα，AR,PR,SHBG),少数生长因子(VEGFA，βNGF,TGFβ1),一些ECM调节剂(MMP1，MMP7)和少数炎性细胞因子(IFNγ，IL10)通过实时RT-PCR分析。结果:ERα转录物明显增多,女性患者Fuchs内皮细胞的AR和SHBG转录物减少，PR转录本没有检测到变化。VEGFA,βNGF和TGFβ1转录在Fuchs内皮中上调，但与性别无关。在Fuchs标本中检测到高MMP1和低MMP7转录本的表达，主要是男性比女性。在女性中观察到IFNγ(Th1)转录表达高于男性。并且在男性中检测到IL10（Th2）转录物的增加趋势。结论：我们的发现清楚地表明，激素受体，生长因子和基质介质以及Th1途径在Fuchs营养不良中占主导地位，显示对女性表型特异的表达模式。激素受体的差异表达和Th1/Th2比值可能促使新理论在体外和体内模型中进行测试。例如使用激素替代品来抵消这种内皮细胞的损失。
