Lens structure in MIP-deficient mice

Abstract

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.