Current and future approaches in the prevention and treatment of diabetic retinopathy

Diabetic retinopathy (DR) is a major cause of blindness worldwide and is the number one cause of blindness in working-age individuals in developed countries. We review the current literature and discuss the pathogenesis, modifying risk factors, genetics, and treatment of DR. Special focus is placed on the rationale and effectiveness of therapeutic modalities, both current and future

Cyclosporin A inhibits caspase-independent death of NGF-deprived sympathetic neurons: a potential role for mitochondrial permeability transition

Opening of the permeability transition pore (PTP) has been implicated as an important mitochondrial event that occurs during apoptosis. We examined the role of the PTP in the well-characterized cell death of rat sympathetic neurons deprived of nerve growth factor (NGF) in vitro. Removal of NGF causes these neurons to undergo either a classic apoptotic cell death or, when treated with a broad-spectrum caspase inhibitor such as boc-aspartyl(OMe)-fluoromethylketone (BAF), a delayed, nonapoptotic cell death. The PTP inhibitor, cyclosporin A (CsA), blocked commitment-to-die in the presence of BAF, as defined by the ability of NGF readdition to rescue cells, but had little effect on commitment-to-die in the absence of BAF. CsA did not have trophic effects on BAF-saved cells, but did block the decrease in mitochondrial membrane potential. These data suggest that PTP opening is a critical event in caspase-independent, nonapoptotic (but not caspase-dependent, apoptotic) death of NGF-deprived rat sympathetic neurons

Alternating metabolic pathways in NGF-deprived sympathetic neurons affect caspase-independent death

Mitochondrial release of cytochrome c in apoptotic cells activates caspases, which execute apoptotic cell death. However, the events themselves that culminate in caspase activation can have deleterious effects because caspase inhibitor–saved cells ultimately die in a caspase-independent manner. To determine what events may underlie this form of cell death, we examined bioenergetic changes in sympathetic neurons deprived of NGF in the presence of a broad-spectrum caspase inhibitor, boc-aspartyl-(OMe)-fluoromethylketone. Here, we report that NGF-deprived, boc-aspartyl-(OMe)-fluoromethylketone–saved neurons rely heavily on glycolysis for ATP generation and for survival. Second, the activity of F0F1 contributes to caspase-independent death, but has only a minor role in the maintenance of mitochondrial membrane potential, which is maintained primarily by electron transport. Third, permeability transition pore inhibition by cyclosporin A attenuates NGF deprivation–induced loss of mitochondrial proteins, suggesting that permeability transition pore opening may have a function in regulating the degradation of mitochondria after cytochrome c release. Identification of changes in caspase inhibitor–saved cells may provide the basis for rational strategies to augment the effectiveness of the therapeutic use of postmitochondrial interventions

Inflammation in Retinal Vein Occlusion

Retinal vein occlusion is a common, vision-threatening vascular disorder. The role of inflammation in the pathogenesis and clinical consequences of retinal vein occlusion is a topic of growing interest. It has long been recognized that systemic inflammatory disorders, such as autoimmune disease, are a significant risk factor for this condition. A number of more recent laboratory and clinical studies have begun to elucidate the role inflammation may play in the molecular pathways responsible for the vision-impairing consequences of retinal vein occlusion, such as macular edema. This improved understanding of the role of inflammation in retinal vein occlusion has allowed the development of new treatments for the disorder, with additional therapeutic targets and strategies to be identified as our understanding of the topic increases

Review Article Inflammation in Retinal Vein Occlusion

Retinal vein occlusion is a common, vision-threatening vascular disorder. The role of inflammation in the pathogenesis and clinical consequences of retinal vein occlusion is a topic of growing interest. It has long been recognized that systemic inflammatory disorders, such as autoimmune disease, are a significant risk factor for this condition. A number of more recent laboratory and clinical studies have begun to elucidate the role inflammation may play in the molecular pathways responsible for the visionimpairing consequences of retinal vein occlusion, such as macular edema. This improved understanding of the role of inflammation in retinal vein occlusion has allowed the development of new treatments for the disorder, with additional therapeutic targets and strategies to be identified as our understanding of the topic increases

Effects of Fermi energy, dot size and leads width on weak localization in chaotic quantum dots

Magnetotransport in chaotic quantum dots at low magnetic fields is investigated by means of a tight binding Hamiltonian on L x L clusters of the square lattice. Chaoticity is induced by introducing L bulk vacancies. The dependence of weak localization on the Fermi energy, dot size and leads width is investigated in detail and the results compared with those of previous analyses, in particular with random matrix theory predictions. Our results indicate that the dependence of the critical flux Phi_c on the square root of the number of open modes, as predicted by random matrix theory, is obscured by the strong energy dependence of the proportionality constant. Instead, the size dependence of the critical flux predicted by Efetov and random matrix theory, namely, Phi_c ~ sqrt{1/L}, is clearly illustrated by the present results. Our numerical results do also show that the weak localization term significantly decreases as the leads width W approaches L. However, calculations for W=L indicate that the weak localization effect does not disappear as L increases.Comment: RevTeX, 8 postscript figures include

Isotropic three-dimensional gap in the iron-arsenide superconductor LiFeAs from directional heat transport measurements

The thermal conductivity k of the iron-arsenide superconductor LiFeAs (Tc ~ 18K) was measured in single crystals at temperatures down to T~50mK and in magnetic fields up to H=17T, very close to the upper critical field Hc2~18T. For both directions of the heat current, parallel and perpendicular to the tetragonal c-axis, a negligible residual linear term k/T is found as T ->0, revealing that there are no zero-energy quasiparticles in the superconducting state. The increase in k with magnetic field is the same for both current directions and it follows closely the dependence expected for an isotropic superconducting gap. There is no evidence of multi-band character, whereby the gap would be different on different Fermi-surface sheets. These findings show that the superconducting gap in LiFeAs is isotropic in 3D, without nodes or deep minima anywhere on the Fermi surface. Comparison with other iron-pnictide superconductors suggests that a nodeless isotropic gap is a common feature at optimal doping (maximal Tc).Comment: 4 pages, 3 figure

Nernst and Seebeck Coefficients of the Cuprate SuperconductorYBa2_2Cu3_3O6.67_{6.67}: A Study of Fermi Surface Reconstruction

The Seebeck and Nernst coefficients $S$ and $\nu$ of the cuprate superconductor YBa$_2$Cu$_3$O$_y$ (YBCO) were measured in a single crystal with doping $p = 0.12$ in magnetic fields up to H = 28 T. Down to T=9 K, $\nu$ becomes independent of field by $H \simeq 30$ T, showing that superconducting fluctuations have become negligible. In this field-induced normal state, $S/T$ and $\nu/T$ are both large and negative in the $T \to 0$ limit, with the magnitude and sign of $S/T$ consistent with the small electron-like Fermi surface pocket detected previously by quantum oscillations and the Hall effect. The change of sign in $S(T)$ at $T \simeq 50$ K is remarkably similar to that observed in La$_{2-x}$Ba$_x$CuO$_4$, La$_{2-x-y}$Nd$_y$Sr$_x$CuO$_4$ and La$_{2-x-y}$Eu$_y$Sr$_x$CuO$_4$, where it is clearly associated with the onset of stripe order. We propose that a similar density-wave mechanism causes the Fermi surface reconstruction in YBCO.Comment: Final version accepted for publication in Phys. Rev. Lett. New title, shorter abstract, minor revision of text and added reference

Mean Free Path and Energy Fluctuations in Quantum Chaotic Billiards

The elastic mean free path of carriers in a recently introduced model of quantum chaotic billiards in two and three dimensions is calculated. The model incorporates surface roughness at a microscopic scale by randomly choosing the atomic levels at the surface sites between -W/2 and W/2. Surface roughness yields a mean free path l that decreases as L/W^2 as W increases, L being the linear size of the system. But this diminution ceases when the surface layer begins to decouple from the bulk for large enough values of W, leaving more or less unperturbed states on the bulk. Consequently, the mean free path shows a minimum of about L/2 for W of the order of the band width. Energy fluctuations reflect the behavior of the mean free path. At small energy scales, strong level correlations manifest themselves by small values of the number of levels variance Sigma^2(E) that are close to Random Matrix Theory (RMT) in all cases. At larger energy scales, fluctuations are below the logarithmic behavior of RMT for l > L, and above RMT value when l < L.Comment: 8 twocolumn pages, seven figures, revtex and epsf macros. To be published in Physical Review B

Phenomenology of the General NMSSM with Gauge Mediated Supersymmetry Breaking

We investigate various classes of Gauge Mediated Supersymmetry Breaking models and show that the Next-to-Minimal Supersymmetric Standard Model can solve the mu-problem in a phenomenologically acceptable way. These models include scenarios with singlet tadpole terms, which are phenomenologically viable, e.g., in the presence of a small Yukawa coupling <~ 10^{-5}. Scenarios with suppressed trilinear A-terms at the messenger scale lead naturally to light CP-odd scalars, which play the r\^ole of pseudo R-axions. A wide range of parameters of such models satisfies LEP constraints, with CP-even Higgs scalars below 114 GeV decaying dominantly into a pair of CP-odd scalars.Comment: 24 pages, 6 figures, typos corrected, reference adde