Howard Hughes Medical Institute, The Jackson Laboratory, Bar Harbor, Maine, USA.
Nat Genet. 2011 Jun;43(6):579-84. doi: 10.1038/ng.813. Epub 2011 May 1.
Angle-closure glaucoma (ACG) is a subset of glaucoma affecting 16 million people. Although 4 million people are bilaterally blind from ACG, the causative molecular mechanisms of ACG remain to be defined. High intraocular pressure induces glaucoma in ACG. High intraocular pressure traditionally was suggested to result from the iris blocking or closing the angle of the eye, thereby limiting aqueous humor drainage. Eyes from individuals with ACG often have a modestly decreased axial length, shallow anterior chamber and relatively large lens, features that predispose to angle closure. Here we show that genetic alteration of a previously unidentified serine protease (PRSS56) alters axial length and causes a mouse phenotype resembling ACG. Mutations affecting this protease also cause a severe decrease of axial length in individuals with posterior microphthalmia. Together, these data suggest that alterations of this serine protease may contribute to a spectrum of human ocular conditions including reduced ocular size and ACG.
闭角型青光眼（ACG）是影响 1600 万人的青光眼的一个亚类。尽管有 400 万人因 ACG 而双眼失明，但 ACG 的致病分子机制仍有待确定。高眼压会导致 ACG。传统上认为高眼压是由于虹膜阻塞或关闭了眼睛的角度，从而限制了房水的排出。ACG 患者的眼睛通常轴向长度略短，前房浅，晶状体相对较大，这些特征容易导致角关闭。在这里，我们表明，以前未识别的丝氨酸蛋白酶（PRSS56）的遗传改变会改变轴向长度，并导致类似于 ACG 的小鼠表型。影响这种蛋白酶的突变也会导致患有后部小眼球症的个体的轴向长度严重下降。总之，这些数据表明，这种丝氨酸蛋白酶的改变可能导致一系列人类眼部疾病，包括眼轴缩小和 ACG。
