Srinivasan Sruthi, Heynen Miriam L, Martell Elizabeth, Ritter Robert, Jones Lyndon, Senchyna Michelle
Centre for Contact Lens Research, School of Optometry, University of Waterloo, Waterloo, Ontario, Canada.
Mol Vis. 2013 May 6;19:970-9. Print 2013.
To quantify the expression of mucin 1, cell surface associated (MUC1) and mucin 16, cell surface associated (MUC16) proteins and messenger ribonucleic acid (mRNA) in a cohort of postmenopausal women (PMW), to explore the relationship between mucin expression, dry eye symptomology, and tear stability.
Thirty-nine healthy PMW (>50 years of age) were enrolled in this study. No specific inclusion criteria were used to define dry eye; instead, a range of subjects were recruited based on responses to the Allergan Ocular Surface Disease Index (OSDI) questionnaire and tear stability measurements as assessed by non-invasive tear breakup time (NITBUT). Tears were collected from the inferior tear meniscus using a disposable glass capillary tube, and total RNA and total protein were isolated from conjunctival epithelial cells collected via impression cytology. Expression of membrane-bound and soluble MUC1 and MUC16 were quantified with western blotting, and expression of MUC1 and MUC16 mRNA was assessed with real-time PCR.
OSDI responses ranged from 0 to 60, and NITBUT ranged from 18.5 to 2.9 s. Only two statistically significant correlations were found: soluble MUC16 protein concentration and MUC16 mRNA expression with OSDI vision related (-0.47; p=0.01) and ocular symptom (0.39; p=0.02) subscores, respectively. Post hoc exploratory analysis on absolute expression values was performed on two subsets of subjects defined as asymptomatic (OSDI≤6, n=12) and moderate to severe symptomatic (OSDI≥20, n=12). The only significant difference between the two subgroups was a significant reduction in MUC16 mRNA expression found in the symptomatic dry eye group (1.52±1.19 versus 0.57±0.44; p=0.03).
A broad exploration of mucin expression compared to either a sign (NITBUT) or symptoms of dry eye failed to reveal compelling evidence supporting a significant relationship, other than a potential association between MUC16 with specific symptoms. Furthermore, comparison of mucin protein and expression levels between the asymptomatic and moderate to severe symptomatic subgroups revealed only one significant difference, a reduction in MUC16 mRNA expression in the symptomatic subgroup.
量化一组绝经后女性(PMW)中细胞表面相关黏蛋白1(MUC1)和细胞表面相关黏蛋白16(MUC16)的蛋白质及信使核糖核酸(mRNA)表达,以探讨黏蛋白表达、干眼症状与泪膜稳定性之间的关系。
本研究纳入了39名年龄大于50岁的健康绝经后女性。未采用特定的纳入标准来定义干眼;相反,根据对爱尔康眼表疾病指数(OSDI)问卷的回答以及通过无创泪膜破裂时间(NITBUT)评估的泪膜稳定性测量结果,招募了一系列受试者。使用一次性玻璃毛细管从下睑泪液弯月面收集泪液,并从通过印迹细胞学收集的结膜上皮细胞中分离总RNA和总蛋白。用蛋白质印迹法定量膜结合型和可溶性MUC1及MUC16的表达,并用实时聚合酶链反应评估MUC1和MUC16 mRNA的表达。
OSDI评分范围为0至60,NITBUT范围为18.5至2.9秒。仅发现两个具有统计学意义的相关性:可溶性MUC16蛋白浓度和MUC16 mRNA表达分别与OSDI视力相关亚评分(-0.47;p = 0.01)和眼部症状亚评分(0.39;p = 0.02)相关。对定义为无症状(OSDI≤6,n = 12)和中度至重度症状(OSDI≥20,n = 12)的两个受试者子集进行了绝对表达值的事后探索性分析。两个亚组之间唯一的显著差异是有症状干眼组中MUC16 mRNA表达显著降低(1.52±1.19对0.57±0.44;p = 0.03)。
与干眼体征(NITBUT)或症状相比,对黏蛋白表达进行广泛探索未能揭示支持显著关系的有力证据,但MUC16与特定症状之间可能存在关联除外。此外,无症状亚组与中度至重度症状亚组之间黏蛋白蛋白和表达水平的比较仅发现一个显著差异,即有症状亚组中MUC16 mRNA表达降低。