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Aldose reductase (AKR1B1) is an NADPH-dependent aldo-keto reductase best known as the rate-limiting enzyme of the polyol pathway. Accelerated glucose metabolism through this pathway has been implicated in diabetic cataract and retinopathy. Some human tissues contain AKR1B1 as well as AKR1B10, a closely related member of the aldo-keto reductase gene superfamily. This opens the possibility that AKR1B10 may also contribute to diabetic complications. The goal of the current study was to characterize the expression profiles of AKR1B1 and AKR1B10 in the human eye. Using quantitative reverse transcriptase-PCR and immunohistochemical staining, we observed expression of both AKR genes in cornea, iris, ciliary body, lens, and retina. Expression of AKR1B1 was the highest in lens and retina, whereas AKR1B10 was the highest in cornea. Lenses from transgenic mice designed for overexpression of AKR1B10 were not significantly different from nontransgenic controls, although a significant number developed a focal defect in the anterior lens epithelium following 6 months of experimentally induced diabetes. However, lenses from AKR1B10 mice remained largely transparent following longterm diabetes. These results indicate that AKR1B1 and AKR1B10 may have different functional properties in the lens and suggest that AKR1B10 does not contribute to the pathogenesis of diabetic cataract in humans. [ABSTRACT FROM AUTHOR]

Background: India is experiencing a rapid health transition with a rising burden of Non-Communicable Diseases (NCDs) and inappropriate lifestyle is the most remarkable risk factor associated to NCDs. Aim & Objective: To assess the prevalence of NCDs and their association with physical activity among urban elderly. Material and methods: A community based cross-sectional study was conducted among 112 geriatric population (≥60 years) in cities of Hyderabad and Secunderabad. The data on medical history, lifestyle, diet and physical activity was obtained using a pre-tested questionnaire. Anthropometric measurements such as weight, height and waist circumference were measured. Intravenous blood samples were collected to estimate the biochemical parameters. Result: About 64.3 % of elderly have been practicing physical activity i.e. predominantly walking, while 35.7% were sedentary. The prevalence of hypertension (87.5%), diabetes (65.3%), central obesity (77.8%) and metabolic syndrome (59.7%) was higher among walkers as compared to non-walkers and the prevalence of metabolic syndrome was significantly (p<0.005) high among the elderly suffering from Cardio Vascular Diseases (CVDs). Conclusion: In general, the prevalence of non-communicable diseases was high among urban geriatric population. Therefore, primordial and primary preventive measures should be adopted during adolescence and early adulthood for the prevention and control of NCDs. [ABSTRACT FROM AUTHOR]

Retinopathy is one of the micro vascular complications of diabetes and can also be observed in pre-diabetic state. However, there are only limited studies available on the pathophysiology of retinopathy in pre-diabetic state and its preventive strategies. In this study, we investigated the retinal functional, structural and molecular alterations using high fructose (HF) induced pre-diabetic rat model and also the protective role of garlic. Feeding of HF to Wistar NIN (WNIN) rats had developed insulin resistance (IR) and impaired glucose tolerance (IGT) by three months, while retinal functional abnormalities by ten months as evidenced by decrease of Electroretinogram (ERG) scotopic, photopic b-wave amplitudes, oscillatory potentials (OPs) when compared to controls. Supplementation of garlic (3%) to HF+G group rats had marginally protected these changes. Elevated expression of glial fibrillary acidic protein (GFAP), vascular endothelial growth factor (VEGF), aldose reductase (AR) and decreased rhodopsin (Rho) in HF group rats as evidenced by immunohistochemistry, immunoblot methods, which were further supported by gene expression studies, indicate the initiation of retinal abnormalities. Increased immunefluorescence signal of carboxymethyl lysine (CML-KLH) and 4-hydroxynanoenol (4-HNE) in retina of HF group rats indicate the association of glycation and oxidative stress, respectively. Early intervention of garlic to HF+G group rats attenuated retinal functional, structural, and molecular abnormalities. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: Cataract is a key factor in the morbidity associated with diabetes. While the pathogenesis of diabetic cataract formation is poorly understood, previous research has identified aldose reductase (ALR2) as a key player. To elucidate a potential role for this enzyme in diabetic cataract formation, we created a series of transgenic mice designed for expression of human ALR2 (AKR1B1) in epithelial and outer cortical fiber cells of the lens. One of the founder lines, designated PAR39, developed an early onset cataract that involved formation of a plaque of cells at the anterior aspect of the lens. These cells appear to separate from the anterior epithelium and undergo a dramatic change that is reminiscent of the epithelial to mesenchymal transition (EMT). We characterized this phenotype in the PAR39 strain by examining rates of cell proliferation and by immunostaining for markers of EMT. Incorporation of the thymidine analog bromodeoxyuridine (BrdU) was used to estimate cell proliferation in two functional areas of the lens epithelium: the mitotically active germinative zone (GZ) and the less proliferative center zone (CZ). Staining cell nuclei with diamido 4′,6-diamidino-2-phenylindole (DAPI) was used to establish a total cell count in the demarcated areas. Lens epithelium in PAR39 transgenic mice demonstrated a decrease in the percentage of BrdU/DAPI staining within the GZ as compared to nontransgenic littermate controls (8.1% vs. 10.9%). A similar decrease in BrdU/DAPI was observed in the CZ (0.6% compared to 3.3%). However, cell density was greater within the GZ of PAR39 mice as compared with nontransgenic controls, while it was not significantly different in the CZ among the two groups. Furthermore, cells associated with the epithelial plaque did not stain positive for BrdU, but were strongly positive for alpha-smooth muscle actin, a classical marker for EMT. These findings suggest that ALR2 over-expression is associated with an alteration in the balance between proliferation and apoptosis of epithelial cells in the mouse lens, and that cells associated with epithelial plaques in the PAR39 lens have features in common with cells undergoing EMT. [Copyright &y& Elsevier]