OBJECTIVEIn diabetes, retinal vascular basement membrane (BM) undergoes significant thickening and compromises vessel function including increased vascular permeability, a prominent lesion of early diabetic retinopathy. In this study we determined whether altered expression and activity of lysyl oxidase (LOX), a cross-linking enzyme, may compromise vascular basement membrane functional integrity under high-glucose (HG) conditions.RESEARCH DESIGN AND METHODSRat retinal endothelial cells (RRECs) grown in normal (5 mmol/l) or HG (30 mmol/l glucose) medium for 7 days were assessed for expression of LOX and proLOX by Western blot analysis and LOX enzyme activity. To determine whether HG alters cellular distribution patterns of LOX and proLOX, immunostaining with respective antibodies was performed. Similarly, cells grown in normal or HG medium were subjected to both LOX inhibition with β-aminopropionitrile (BAPN) and by small interfering RNA knockdown, and respectively examined for cell monolayer permeability. Additionally, retinas of streptozotocin (STZ)-induced diabetic rats were analyzed to determine if diabetes altered LOX expression.RESULTSWestern blot analysis revealed significantly increased LOX and proLOX expression in cells grown in HG medium compared with those grown in normal medium. The increased LOX level was strikingly similar to LOX upegulation in the diabetic retinas. In cells grown in HG medium, LOX activity and cell monolayer permeability was significantly increased, as were LOX and proLOX immunostaining. Small interfering RNA- or BAPN–induced-specific blockage of LOX expression or activity, respectively, reduced cell monolayer permeability.CONCLUSIONSHG-induced increased LOX expression and activity compromises barrier functional integrity, a prominent lesion of diabetic retinopathy.

Future applications for emerging AlN semiconductor electronics and optoelectronics are facilitated by emerging doping technologies enabled by low temperature, non-equilibrium epitaxy. Defect and impurity compensation can be reduced by controlling the surface chemistry with reducing compensating vacancy concentrations being a key driver for lower temperature growth. Contrary to common understanding, low temperature, metal-rich vacuum processes are shown to have higher diffusion lengths than high temperature nitrogen-rich methods. This feature can be utilized to inhibit silicon-DX center formation without compromises in crystal quality. First principles calculations identify the valence split-off band as the dominant hole band contributing to impurity band formation (as opposed to the heavy and light hole bands in other nitrides). This anomalous band structure causes an impurity band to form at dopant concentrations similar to GaN even though AlN has a deeper isolated acceptor energy and results in hole mobilities that are substantially higher than possible in GaN. AlN hole concentrations of ∼4.4 × 1018 cm−3 and 0.045 Ω cm resistivity and electron concentrations of ∼6 × 1018 cm−3 and ∼0.02 Ω cm resistivity are shown and offer substantial promise for future generations of AlN bipolar electronic and optical devices.

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