Biomedical subjects

Kristin J Al-Ghoul

Publications and source records attributed to Kristin J Al-Ghoul.

3 recordsLinked to original sources

PubMed2003

Morphology and organization of posterior fiber ends during migration.

PURPOSE: To characterize structural parameters of the basal membrane complex (BMC) and to determine the arrangement and organization of posterior fiber ends during elongation/migration in lenses with branched sutures. METHODS: Lenses from normal, juvenile (4-6 week old) Sprague-Dawley rats (n=16) were utilized. Posterior fiber ends were assessed on both whole mounts of lens capsules and on decapsulated lenses. The size, shape and organization of migrating fiber ends was assessed by scanning electron microscopy (SEM) and laser scanning confocal microscopy (LSCM) along the entire posterior surface. The area of the BMC was measured using image analysis software and subjected to statistical analysis. RESULTS: Posterior fiber ends had a characteristic regional arrangement during elongation and migration along the capsule. These regions were termed the equatorial, the lateral-posterior (posterior from the equator to within 150 microm of the sutures), the peri-sutural (150 microm surrounding the sutures), and the sutural. The area of fiber ends (seen by SEM) was compared to the area of fluorescent F-actin profiles (seen by LSCM). There was no significant difference (p=0.324) between the average basal end area (40.21 microm2) and the average area of F-actin profiles (40.65 microm2). The average fiber end area in the lateral-posterior, peri-sutural, and sutural regions was 63.19 microm2, 71.95 microm2, and 25.75 microm2, respectively. In the equatorial region, footprints were aligned in rows oriented toward the posterior pole, consistent with the arrangement of straight, meridional rows. Initially, fiber ends within the lateral-posterior region were arranged in short irregular rows having variable orientation with respect to the posterior pole. The remainder of these ends were randomly arranged. In the peri-sutural region, fiber ends approaching suture branches were aligned in short rows oriented at angles to the posterior pole. At the sutures, fiber ends appeared to become rounded, presumably during detachment from the capsule. CONCLUSIONS: The results confirm that F-actin profiles delineate the BMC of posterior fiber ends. Furthermore, the average area, shape and arrangement of fiber ends varies in a predictable pattern during migration. The data suggests that elongating fiber ends follow defined migration patterns along the posterior capsule to their sutural destinations. This controlled process is crucial to the formation of ordered suture patterns, thereby minimizing their adverse effects on lens optical quality.

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PubMed2003

Lens structure in MIP-deficient mice.

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.

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PubMed2003

Discordant expression of the sterol pathway in lens underlies simvastatin-induced cataracts in Chbb: Thom rats.

Simvastatin rapidly induced cataracts in young Chbb:Thom (CT) but not Sprague Dawley (SD) or Hilltop Wistar (HW) rats. Oral treatment for 14 but not 7 days committed CT rat lenses to cataract formation. The cholesterol to phospholipid molar ratio in lenses of treated CT rats was unchanged. Differences between strains in serum and ocular humor levels of simvastatin acid poorly correlated with susceptibility to cataracts. No significant differences were found between rat strains in the capacity of simvastatin acid to inhibit lens-basal sterol synthesis. Prolonged treatment with simvastatin comparably elevated HMG-CoA reductase protein and enzyme activity in lenses of both cataract resistant and sensitive strains. However, in contrast to SD and HW rats, where sterol synthesis was markedly increased, sterol synthesis in CT rat lenses remained at baseline. Discordant expression of sterol synthesis in CT rats may be due to inadequate upregulation of lens HMG-CoA synthase. HMG-CoA synthase protein levels, and to a much lesser extent mRNA levels, increased in lens cortex of SD but not CT rats. Because upregulation of the sterol pathway may result in increased formation of isoprene-derived anti-inflammatory substances, failure to upregulate the pathway in CT rat lenses may reflect an attenuated compensatory response to injury that resulted in cataracts.

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