Rebecca Manohar, Sripriya Krishnamoorthy, Bharathselvi M, Shantha B, Vijaya Lingam, Angayarkanni Narayanasamy
RS Mehta Jain Dept. of Biochemistry and Cell Biology, KBIRVO Block, Vision Research Foundation, Chennai, 600006, India; Tamil Nadu Dr. MGR Medical University, Guindy, Chennai, 600032, India.
Smt. Jadhavbai Nathamal Singhvee Glaucoma Services, Medical Research Foundation, Sankara Nethralaya, Chennai, 600006, India.
Exp Eye Res. 2022 Feb;215:108898. doi: 10.1016/j.exer.2021.108898. Epub 2021 Dec 17.
Pseudoexfoliation syndrome (PXF) is an idiopathic disease with a high prevalence rate. The elastosis disorder is contributed by genetic and non-genetic factors. Elastin dysregulation associated with the disease mechanism is incompletely understood. This study evaluated the molecules of the elastogenesis machinery in PXF. Lens capsule and aqueous humor (aqH) samples (age/sex-matched) were collected from the eyes with PXF alone and PXF with glaucoma (PXF-G) undergoing Extra Capsular Cataract Extraction (ECCE) surgery. The Elastin turnover was assessed by estimating Desmosine levels in the lens capsules by HPLC analysis. Expression of elastogenesis genes [EMILIN1, CLU, FBN1, FN1, FBLN5, FBLN4 and LOXL1] were evaluated in the lens capsule by qPCR while the proteins were assessed in aqH by western blot analysis. The Desmosine content in the lens capsules were 3-fold and 6-fold elevated in PXF (P = 0.02) and PXF-G (P = 0.01) respectively compared to the cataract-alone, indicating increased elastin degradation. A significant increase in the transcript levels of the CLU, FBLN4, EMILIN1, FBLN5, FN1, FBN1, LOXL1 along with significant changes in protein expression of CLU, FBLN5, FBN1 and LOXL1 signified up-regulation of the elastogenesis machinery. The study provides direct evidence of augmented elastin degradation and turnover in the lens capsule of PXF marked by increased Desmosine content and the expression of proteins involved in mature elastin formation.
假性剥脱综合征（PXF）是一种发病率较高的特发性疾病。这种弹性组织变性疾病由遗传和非遗传因素共同导致。与疾病机制相关的弹性蛋白调节异常尚未完全明确。本研究评估了PXF中弹性蛋白生成机制的相关分子。从仅患有PXF以及患有PXF合并青光眼（PXF - G）且正在接受白内障囊外摘除术（ECCE）的患者眼中收集（年龄/性别匹配的）晶状体囊膜和房水（aqH）样本。通过高效液相色谱分析估计晶状体囊膜中的异锁链素水平来评估弹性蛋白的周转率。通过qPCR评估晶状体囊膜中弹性蛋白生成基因[EMILIN1、CLU、FBN1、FN1、FBLN5、FBLN4和LOXL1]的表达，同时通过蛋白质印迹分析评估房水中的蛋白质。与单纯白内障相比，PXF组（P = 0.02）和PXF - G组（P = 0.01）晶状体囊膜中的异锁链素含量分别升高了3倍和6倍，表明弹性蛋白降解增加。CLU、FBLN4、EMILIN1、FBLN5、FN1、FBN1、LOXL1的转录水平显著增加，同时CLU、FBLN5、FBN1和LOXL1的蛋白质表达也发生显著变化，这表明弹性蛋白生成机制上调。该研究提供了直接证据，证明PXF晶状体囊膜中弹性蛋白降解和周转率增加，其特征是异锁链素含量增加以及参与成熟弹性蛋白形成的蛋白质表达增加。
