Aberrant basal fiber end migration underlies structural malformations in a streptozotocin-induced diabetic rat model

Abstract

This study characterized early structural changes at posterior fiber ends in the crystalline lens after diabetic induction. Wistar rats (n=49), randomized into one naïve control group and four experimental groups, were rendered diabetic via streptozotocin injection. Animals were euthanized at 1 week intervals, blood glucose levels recorded and lenses were evaluated grossly, by SEM and by confocal microscopy. Indices were developed to assess structural alterations and for statistical correlations between the scores and the duration of hyperglycemic exposure as well as blood glucose levels. Average blood glucose levels increased progressively from 98.5 mg/dL (controls) to 331.4 mg/dL (4 weeks). Diabetic lenses displayed abnormal suture sub-branches and opacity formation beginning late in the first week post-injection and rapidly progressing in severity through four weeks. SEM analyses showed gradual elongation of fiber ends and filopodia which comprised a disorganized configuration and a loss of recognizable migration patterns. Structural alterations culminated in foci of fiber degeneration by the third to fourth weeks. The F-actin distribution at basal fiber ends was significantly altered as compared to naïve controls. Cadherin distribution was altered as compared to controls, but largely at later time points. The grading system clearly shows increased structural compromise with elevated blood glucose levels in streptozotocin-induced diabetes. Further, although the initial rise in blood glucose levels was associated with pathological changes, their progression depended to a larger extent on continued hyperglycemic exposure. The data suggests that hyperglycemia initially disrupts fiber end migration, resulting in structural alterations and eventual fiber degeneration.

Effect of Potentilla Fulgens L. on Selected Enzyme Activities and Altered Tissue Morphology in Diabetic Mice

“…This is in line with previous reports that hyperglycemic states adversely affect the lens fiber and morphology patterns, resulting in structural alterations. 54 In diabetic mice treated with the P. fulgens extract, a regular alignment of the lens fibers was observed. Although the lens segments were not as compact as observed in normal lenses, the honeycomb-like pattern with a regularly aligned array was seen to be regular, and the alterations in the fiber pattern were minimized in P. fulgens extract-treated diabetic mice.…”

Nicotine Exposure Exacerbates Development of Cataracts in a Type 1 Diabetic Rat Model

“…Zhang et al 2008 [ 13 ] observed initial stages of cataract formation macroscopically 3 weeks after induction of diabetes and whole lens opacity after 12 weeks. Additionally, scanning electron microscopy revealed structural anomalies in diabetic rat lenses as early as one week after STZ injection [ 14 ]. Thus, a hyperglycemic environment results in greater susceptibility of ocular tissue to further damage from environmental factors and stress.…”