Safari Iman, Suri Fatemeh, Haji-Seyed-Javadi Ramona, Yazdani Shahin, Elahi Elahe
School of Biology, University College of Science, University of Tehran, Tehran, Iran.
Ophthalmic Res. 2016 Jul;56(2):98-103. doi: 10.1159/000443508. Epub 2016 Mar 17.
The aim of this work was to assess the possible effects of CYP1B1 mutations on the extracellular matrix (ECM) in glaucoma patients. CYP1B1 mutations are the cause of disease in a notable fraction of primary congenital glaucoma (PCG) patients and in a smaller fraction of primary open angle glaucoma (POAG) patients.
The study was performed on a glaucoma family with the common homozygous p.Gly61Glu CYP1B1 mutation. The father was affected with POAG and three siblings had PCG. Microscopy was performed on the skin of the father and one son, as well as controls. Immunohistochemical studies were done using anti-CYP1B1 and anti-fibrillin-1 antibodies. Fibrillin-1 served as a marker for the ECM, and electron microscopy was also performed.
CYP1B1 expression patterns were the same in the patients and controls. However, microfibrils that are associated with fibrillin-1 were less abundant and more fragmented in both patients. Electron microscopy showed disturbed collagen fibers only in the PCG patient.
The p.Gly61Glu mutation in CYP1B1 affects the ECM structure. This implies that the ECM of the trabecular meshwork may also be disrupted in a manner that affects aqueous humor flow resulting in increased intraocular pressure and contributing to the glaucoma phenotype.
本研究旨在评估CYP1B1突变对青光眼患者细胞外基质（ECM）的潜在影响。CYP1B1突变是相当一部分原发性先天性青光眼（PCG）患者以及一小部分原发性开角型青光眼（POAG）患者的致病原因。
对一个患有常见纯合子p.Gly61Glu CYP1B1突变的青光眼家族进行了研究。父亲患有POAG，三个兄弟姐妹患有PCG。对父亲和一个儿子的皮肤以及对照组进行了显微镜检查。使用抗CYP1B1和抗原纤维蛋白-1抗体进行免疫组织化学研究。原纤维蛋白-1作为ECM的标志物，还进行了电子显微镜检查。
患者和对照组中CYP1B1的表达模式相同。然而，在两名患者中，与原纤维蛋白-1相关的微原纤维数量较少且更加碎片化。电子显微镜检查仅在PCG患者中显示胶原纤维紊乱。
CYP1B1中的p.Gly61Glu突变影响ECM结构。这意味着小梁网的ECM也可能以影响房水流动的方式受到破坏，导致眼压升高并促成青光眼表型。
