Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, 660 S. Euclid Ave, Box 8096, St. Louis, MO 63117, USA
St Louis College of Pharmacy, Department of Basic Sciences, 4588 Parkview Place, St. Louis, MO 63110, USA.
Dis Model Mech. 2019 Jan 25;12(1):dmm037283. doi: 10.1242/dmm.037283.
Fibrillin is an evolutionarily ancient protein that lends elasticity and resiliency to a variety of tissues. In humans, mutations in fibrillin-1 cause Marfan and related syndromes, conditions in which the eye is often severely affected. To gain insights into the ocular sequelae of Marfan syndrome, we targeted in mouse lens or non-pigmented ciliary epithelium (NPCE). Conditional knockout of in NPCE, but not lens, profoundly affected the ciliary zonule, the system of fibrillin-rich fibers that centers the lens in the eye. The tensile strength of the fibrillin-depleted zonule was reduced substantially, due to a shift toward production of smaller caliber fibers. By 3 months, zonular fibers invariably ruptured and mice developed ectopia lentis, a hallmark of Marfan syndrome. At later stages, untethered lenses lost their polarity and developed cataracts, and the length and volume of mutant eyes increased. This model thus captures key aspects of Marfan-related syndromes, providing insights into the role of fibrillin-1 in eye development and disease.
纤维连接蛋白是一种进化上古老的蛋白质，为多种组织提供弹性和韧性。在人类中，纤维连接蛋白 1 的突变导致马凡氏综合征和相关综合征，这些疾病常严重影响眼睛。为了深入了解马凡氏综合征的眼部后遗症，我们在小鼠晶状体或非色素睫状上皮（NPCE）中靶向 。条件性敲除 NPCE 中的 ，而不是晶状体中的 ，会严重影响睫状带，即纤维连接蛋白丰富纤维的系统，该系统将晶状体固定在眼睛中。由于较小口径纤维的产生增加，纤维连接蛋白耗尽的睫状带的拉伸强度大大降低。到 3 个月时，睫状带纤维不可避免地破裂，小鼠出现晶状体异位，这是马凡氏综合征的一个标志。在后期阶段，未固定的晶状体失去极性并形成白内障，并且突变体眼睛的长度和体积增加。因此，该模型捕获了与马凡氏综合征相关的综合征的关键方面，深入了解了纤维连接蛋白 1 在眼睛发育和疾病中的作用。
