Al-Ghoul Kristin J, Kirk Tyler, Kuszak Adam J, Zoltoski Rebecca K, Shiels Alan, Kuszak Jer R
Department of Anatomy and Cell Biology, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612, USA.
Anat Rec A Discov Mol Cell Evol Biol. 2003 Aug;273(2):714-30. doi: 10.1002/ar.a.10080.
In this study we used correlative light, scanning, and transmission (freeze-etch) electron microscopy to characterize lens structure in normal mice and compare it with that in mice deficient in the major intrinsic protein (MIP) of fiber cells. Grossly, wild-type lenses were transparent and had typical Y sutures at all of the ages examined. These lenses had fibers of uniform shape (hexagonal in cross section) arranged in ordered concentric growth shells and radial cell columns. In addition, these fibers had normal opposite end curvature and lateral interdigitations regularly arrayed along their length. Ultrastructural evaluation of these fibers revealed anterior and posterior end segments characterized by square array membrane on low-amplitude wavy fiber membrane. Approximately 13% of the equatorial or mid segments of these same fibers were specialized as gap junctions (GJs). In contrast, heterozygote lenses, while initially transparent at birth, were translucent by 3 weeks of age, except for a peripheral transparent region that contained fibers in the early stages of elongation. This degradation in clarity was correlated with abnormal fiber structure. Specifically, although the mid segment of these fibers was essentially normal, their end segments lacked normal opposite end curvature, were larger than normal, and had a distinct non-hexagonal shape. As a result, these fibers failed to form typical Y sutures. Furthermore, the nuclear fibers of heterozygote lenses were even larger and lacked any semblance of an ordered packing arrangement. Grossly, homozygote lenses were opaque at all ages examined, except for a peripheral transparent region that contained fibers in the early stages of elongation. All fibers from homozygote lenses lacked opposite end curvature, and thus failed to form any sutures. Also, these fibers were essentially devoid of interlocking devices, and only 7% of their mid segment was specialized as GJs. The results of this study suggest that MIP has essential roles in the establishment and maintenance of uniform fiber structure, and the organization of fibers, and as such is essential for lens function.
在本研究中，我们使用相关光镜、扫描电镜和透射（冷冻蚀刻）电镜来表征正常小鼠的晶状体结构，并将其与纤维细胞主要内在蛋白（MIP）缺陷小鼠的晶状体结构进行比较。大体上，野生型晶状体在所有检测年龄均透明，且有典型的Y形缝线。这些晶状体具有形状均匀（横截面为六边形）的纤维，排列成有序的同心生长层和放射状细胞柱。此外，这些纤维具有正常的相对端曲率，并且沿其长度方向有规则排列的侧向交错。对这些纤维的超微结构评估显示，其前端和后端节段的特征是在低振幅波浪状纤维膜上有方形排列的膜。这些相同纤维的赤道或中段约13%特化为缝隙连接（GJ）。相比之下，杂合子晶状体虽然出生时最初是透明的，但到3周龄时变得半透明，除了一个外围透明区域，该区域含有处于伸长早期阶段的纤维。这种透明度的下降与异常的纤维结构相关。具体而言，尽管这些纤维的中段基本正常，但其端节段缺乏正常的相对端曲率，比正常的大，且具有明显的非六边形形状。结果，这些纤维未能形成典型的Y形缝线。此外，杂合子晶状体的核纤维甚至更大，且缺乏任何有序堆积排列的 semblance。大体上，纯合子晶状体在所有检测年龄均不透明，除了一个外围透明区域，该区域含有处于伸长早期阶段的纤维。来自纯合子晶状体的所有纤维都缺乏相对端曲率，因此未能形成任何缝线。此外，这些纤维基本上没有互锁装置，其中段只有7%特化为GJ。本研究结果表明，MIP在均匀纤维结构的建立和维持以及纤维的组织中具有重要作用，因此对晶状体功能至关重要。
