Stein Eye Institute, Department of Ophthalmology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Genes (Basel). 2021 Nov 16;12(11):1802. doi: 10.3390/genes12111802.
Glaucoma is the leading cause of irreversible blindness worldwide, with elevated intraocular pressure (IOP) as the only known modifiable risk factor. Trabecular meshwork (TM)-inducible myocilin (the gene) was the first to be identified and linked to juvenile and primary open-angle glaucoma. It has been suggested that mutations in the gene and the aggregation of mutant myocilin in the endoplasmic reticulum (ER) of TM may cause ER stress, resulting in a reduced outflow of aqueous humor and an increase in IOP. We selected 20 mutations with experimentally determined melting temperatures of mutated myocilin proteins. We included 40 published studies with at least one glaucoma patient with one of these 20 mutations and information on age at glaucoma diagnosis. Based on data from 458 patients, we found that a statistically significant but weak correlation was present between age and melting temperature based on various assumptions for age. We therefore conclude that genetic analysis of mutations alone cannot be used to accurately predict age at glaucoma diagnosis. However, it might be an important prognostic factor combined with other clinical factors for critical and early detection of glaucoma.
青光眼是全球导致不可逆性失明的主要原因，而眼内压（IOP）升高是唯一已知可改变的危险因素。小梁网（TM）诱导肌球蛋白（该基因）是第一个被发现并与青少年和原发性开角型青光眼相关的基因。据推测，该基因的突变和突变肌球蛋白在 TM 内质网（ER）中的聚集可能导致 ER 应激，从而导致房水流出减少和 IOP 升高。我们选择了 20 个具有实验确定的突变肌球蛋白蛋白熔点的突变。我们纳入了 40 项已发表的研究，这些研究至少有一名青光眼患者携带这 20 个突变中的一个，并且有关于青光眼诊断时年龄的信息。基于 458 名患者的数据，我们发现，基于对年龄的各种假设，年龄与熔点之间存在统计学上显著但较弱的相关性。因此，我们得出结论，仅对突变进行基因分析不能准确预测青光眼的诊断年龄。然而，它可能是一个重要的预后因素，与其他临床因素结合使用，有助于对青光眼进行关键和早期检测。
