Aldose reductase (AR) is thought to play a role in the pathogenesis of diabetic eye diseases, including cataract and retinopathy. However, not all diabetics develop ocular complications. Paradoxically, some diabetics with poor metabolic control appear to be protected against retinopathy, while others with a history of excellent metabolic control develop severe complications. These observations indicate that one or more risk factors may influence the likelihood that an individual with diabetes will develop cataracts and/or retinopathy. We hypothesize that an elevated level of AR gene expression could confer higher risk for development of diabetic eye disease. To investigate this hypothesis, we examined the onset and severity of diabetes-induced cataract in transgenic mice, designated AR-TG, that were either heterozygous or homozygous for the human AR (AKR1B1) transgene construct. AR-TG mice homozygous for the transgene demonstrated a conditional cataract phenotype, whereby they developed lens vacuoles and cataract-associated structural changes only after induction of experimental diabetes; no such changes were observed in AR-TG heterozygotes or nontransgenic mice with or without experimental diabetes induction. We observed that nondiabetic AR-TG mice did not show lens structural changes even though they had lenticular sorbitol levels almost as high as the diabetic AR-TG lenses that showed early signs of cataract. Over-expression of AR led to increases in the ratio of activated to total levels of extracellular signal-regulated kinase (ERK1/2) and c-Jun N-terminal (JNK1/2), which are known to be involved in cell growth and apoptosis respectively. After diabetes induction, AR-TG but not WT controls had decreased levels of phosphorylated as well as total ERK1/2 and JNK1/2 compared to their nondiabetic counterparts. These results indicate that high AR expression in the context of hyperglycemia and insulin deficiency may constitute a risk factor that could predispose the lens to disturbances in signaling through the ERK and JNK pathways and thereby alter the balance of cell growth and apoptosis that is critical to lens transparency and homeostasis.

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Experimental true stress–true strain data of Nimonic C-263 alloy in solution treated as well as aged condition have been analysed using different flow relationships. Ludwigson relationship provides the best fit of the data for all the conditions investigated. The transition in macroscopic flow behaviour of the alloy with plastic strain, in solution treated condition, can be correlated with the transition in deformation mode from low strain regime to high strain regime. Although aging does not appear to alter the macroscopic flow behaviour, it causes a considerable change in flow parameters of the Ludwigson relationship and substructural evolution. On the other hand, the effect of sheet thickness is marginal. The flow data of the aged alloys fitted according to Ludwigson model not only yield a unique set of flow parameters for each aging condition but also exhibit a systematic trend with aging time. The transition in macroscopic flow behaviour of the alloy with strain, in aged conditions, can be correlated with a change in dislocation mechanism from dislocation–precipitate interaction at lower strains to dislocation–dislocation interaction at higher strains leading to formation of a dense dislocation tangled networks in the matrix regions surrounding the precipitates. The alloy in both solution treated and aged conditions exhibits three fairly distinct stages of strain hardening. The strain hardening rate decreases in regime I, remains constant in regime II and begins to fall again in regime III. Furthermore, it is observed that the alloy specimen with longitudinal orientation (L, i.e. parallel to rolling direction), exhibits marginally highest strain hardening rates, while specimens with long transverse orientation exhibit lowest strain hardening rates both in solution treated and aged conditions. However, for all other in-plane orientations (i.e. L+30°, L+45° and L+60°), the strain hardening rate data are fairly very close and lie in between those of longitudinal and long transverse orientations.