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A. Joy, M. S. Currie, S. T. Donohue, K. J. Al-Ghoul; The Severity of Structural Abnormalities in the Lens Is Correlated With Blood Glucose Levels in a Streptozotocin (STZ)-Induced Diabetic Rat Model. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2288. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Our studies have shown that altered morphology and arrangement of lens fiber ends in STZ diabetes rats are associated with abnormal suture sub-branch and opacity formation. The present study characterizes the structure of posterior fiber ends in relation to blood glucose levels.
Wistar rats (n=50) were randomized into 5 groups, four of which received a single 75 mg/kg intravenous dose of STZ; the remaining group served as a naïve control. Animals were euthanized at 1, 2, 3 and 4 weeks post-injection, blood glucose levels recorded, lenses removed and photographed to evaluate suture sub-branches and lens opacities. Lenses were also evaluated by scanning electron microscopy (SEM) to assess fiber end morphology. Confocal microscopy was used on contralateral lenses to localize F-actin and pan-cadherin. A grading system was developed to compare suture sub-branches, lens opacities, fiber end morphology, F-actin arrangement, cadherin distribution and blood glucose levels. The system consisted of four blocks of numerical indices, each with clearly defined subsets that indicated increasing complexity of structural abnormalities.
The recorded blood glucose levels showed a progressive increase, from a mean of 88.44 mg/dL in the naïve controls to 306.25 mg/dL by 4 weeks post-injection. The lenses revealed suture sub-branches and opacity formation beginning in the first week post-injection and rapidly progressing in severity through four weeks. SEM analyses showed changes to fiber ends, beginning as a disorganized pattern of swirled ends in the 1st week and progressing to foci of fiber structure loss by 3-4 weeks. Cadherin in normal lenses was localized to the lateral domains and fiber end footprints by confocal microscopy. By the 4th week, the cadherin distribution around the footprints showed decreased signal and an irregular pattern. Cadherin in the lateral domain was largely unaffected. F-actin rearrangements progressed in severity from 1 through 4 weeks post-injection. The grading system clearly shows an increased structural compromise with increased blood glucose levels in STZ diabetes.
A defined altered pattern of fiber end morphology, cadherin distribution and F-actin arrangement can be expected at each level of grading. The initial rise in blood glucose levels in the first two weeks post-injection is associated with pathological changes, but the progression of these changes over the next two weeks depends to a larger extent on continued hyperglycemic exposure.
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