Effects of anti-glaucoma medications on gangion cell survival: the DBA/2J mouse model

AbstractWe studied whether several agents, approved or undergoing trials in human glaucoma, were effective in preventing ganglion cell loss in the DBA/2J mouse. Adult DBA/2J mice were treated with timolol, pilocarpine, brimonidine, dorzolamide, or NMDA-receptor antagonist memantine. Surviving retinal ganglion cells of treated and control mice were retrogradely labeled with fluorogold and counted after whole mount preparation. In treated mice, only memantine and timolol had significant effects on retinal ganglion cell survival (P<0.0001, analysis of variance). Brimonidine was lethal to these mice, and these retinae were not analyzed further. The DBA/2J mouse represents a promising candidate for further experimentation in ocular hypertension

An in vivo evaluation of Brilliant Blue G in animals and humans

Background/Aims: To evaluate the retinal toxicity of Brilliant Blue G (BBG) following intravitreal injection in rat eyes and examine the biocompatibility and the staining properties in humans.Methods: BBG was injected into the 11 rat eyes to evaluate toxic effects with balanced salt solution (BSS) serving as control. Retinal toxicity was assessed by retinal ganglion cell (RGC) counts and by light microscopy 7 days later. In addition, BBG was applied during vitrectomy for macular hole (MH) (n = 15) or epiretinal membranes (ERM) (n = 3) in a prospective, non-comparative consecutive series of patients. Before and after surgery, all patients underwent a complete clinical examination including measurement of best corrected visual acuity (VA) and intraocular pressure, perimetry, fundus photography and optical coherence tomography. Patients were seen 1 day before surgery and then in approximately four weeks intervals.Results: No significant reduction in RGC numbers and no morphological alterations were noted. A sufficient staining of the internal limiting membrane (ILM) was seen in patients with MH, while the staining pattern in ERM cases was patchy, indicating that parts of the ILM were peeled off along with the ERM in a variable extent. All MHs could be closed successfully. VA improved in 10 eyes (56%; 8/15 MH patients, 2/3 ERM patients), was unchanged in four eyes (22%; all MH patients) and was reduced in four eyes (22%; 3/15 MH, 1/3 ERM). No toxic effects attributable to the dye were noted during patient follow-up. The ultrastructure of tissue harvested during surgery was unremarkable.Conclusion: Brilliant Blue provides a sufficient and selective staining of the ILM. No retinal toxicity or adverse effects related to the dye were observed in animal and human studies. The long-term safety of this novel dye will have to be evaluated in larger patient series and a longer follow-up

Tryptophan and Kynurenine Pathway Metabolites in Animal Models of Retinal and Optic Nerve Damage: Different Dynamics of Changes

Kynurenines, products of tryptophan (TRP) metabolism, display neurotoxic (e.g., 3-hydroxykynurenine; 3-HK), or neuroprotective (e.g., kynurenic acid; KYNA) properties. Imbalance between the enzymes constituting the kynurenine pathway (KP) plays a role in several disease, including neurodegeneration. In this study, we track changes in concentrations of tryptophan and its selected metabolites after damage to retinal ganglion cells and link this data with expression of KP enzymes. Brown-Norway rats were subjected to intravitreal N-methyl-D-aspartate (NMDA) injection or partial optic nerve crush (PONC). Retinas were collected 2 and 7 days after the completion of PONC or NMDA injection. Concentrations of TRP, kynurenine (KYN), and KYNA were determined by high performance liquid chromatography (HPLC). Data on gene expression in the rat retina were extracted from GEO, public microarray experiments database. Two days after NMDA injection concentration of TRP decreased, while KYN and KYNA increased. At day 7 compared to day 2 decrease of KYN, KYNA and further reduction of TRP concentration were observed, but on day 7 KYN concentration was still elevated when compared to controls. At day 2 and 7 after NMDA injection no statistically significant alterations of 3-HK were observed. TRP and 3-HK concentration was higher in PONC group than in controls. However, both KYN and KYNA were lower. At day seven concentration of TRP, 3-HK, and KYN was higher, whereas concentration of KYNA declined. In vivo experiments showed that retinal damage or optic nerve lesion affect TRP metabolism via KP. However, the pattern of changes in metabolite concentrations was different depending on the model. In particular, in PONC KYNA and KYN levels were decreased and 3-HK elevated. These observations correspond with data on expression of genes encoding KP enzymes assessed after optic nerve crush or transection. After intraorbital optic nerve crush downregulation of KyatI and KyatIII between 24 h and 3 days after procedure was observed. Kmo expression was transiently upregulated (12 h after the procedures). After intraorbital optic nerve transsection (IONT) Kmo expression was upregulated after 48 h and 7 days, KyatI and KyatIII were downregulated after 12, 48 h, 7 days and upregulated after 15 days. Collected data point to the conclusion that development of therapeutic strategies targeting the KP could be beneficial in diseases involving retinal neurodegeneration

First analysis of anisotropic flow with Lee--Yang zeroes

We report on the first analysis of directed and elliptic flow with the new method of Lee--Yang zeroes. Experimental data are presented for Ru+Ru reactions at 1.69 AGeV measured with the FOPI detector at SIS/GSI. The results obtained with several methods, based on the event-plane reconstruction, on Lee--Yang zeroes, and on multi-particle cumulants (up to 5th order) applied for the first time at SIS energies, are compared. They show conclusive evidence that azimuthal correlations between nucleons and composite particles at this energy are largely dominated by anisotropic flow.Comment: 5 pages, 3 figures, submitted to Phys. Rev. C Rapid Co

Signal coupling and signal integrity in multi-strip Resistive Plate Chambers used for timing applications

We have systematically studied the transmission of electrical signals along several 2-strip Resistive Plate Chambers (RPCs) in the frequency range $f=0.1-3.5$GHz. Such a range was chosen to fully cover the bandwidth associated to the very short rise-times of signals originated in RPCs used for sub-100ps timing applications. This work conveys experimental evidence of the dominant role of modal dispersion in counters built at the 1 meter scale, a fact that results in large cross-talk levels and strong signal shaping. It is shown that modal dispersion appears in RPCs due to the intrinsic unbalance between the capacitive and the inductive coupling $C_m/C_o \neq L_m/L_o$. A practical way to restore this symmetry has been introduced (hereafter `electrostatic compensation'), allowing for a cross-talk suppression factor of around $\times 12$ and a rise-time reduction by 200ps. Under conditions of compensation the signal transmission is only limited by dielectric losses, yielding a length-dependent cutoff frequency of around 1GHz per 2 meter for typical float glass -based RPCs ($\tan \delta|_{glass} = 0.025\pm0.005$). It is further shown that `electrostatic compensation' can be achieved for an arbitrary number of strips as long as the nature of the coupling is `short-range', that is an almost exact assumption for typical strip-line RPCs. Evidence for deviations from the dominant TEM propagation mode has been observed, although they seem to have negligible influence in practical signal observables. This work extends the bandwidth of previous studies by a factor of almost $\times 20$.Comment: submitted to NI

Single-Dose Intravenous Toxicity Study of IRDye 800CW in Sprague-Dawley Rats

Objective: Fluorophore-labeled contrast imaging agents are moving toward clinical use for a number of applications. The near-infrared dye IRDye 800CW is frequently used in its N-hydroxysuccinamide (NHS) ester form for labeling these agents. Following conjugation or breakdown of a labeled ligand, excess NHS ester is converted to the carboxylate form. To prepare for clinical use as a near-infrared fluorophore, a toxicity study was conducted on IRDye 800CW carboxylate. Methods: Male and female Sprague–Dawley rats were given a single intravenous or intradermal administration of IRDye 800CW carboxylate; Indocyanine Green was used as a comparative control. Animals were injected with varying doses of the test and control articles and observed for up to 14 days. Clinical chemistry, hematological, and pharmacokinetic analyses were performed on subgroups of animals. Organs were analyzed for content of the test article. Tissues were analyzed microscopically for pathological changes. Results: Based on hematologic, clinical chemistry, and histopathologic evaluation, single administration of IRDye 800CW carboxylate intravenously at dose levels of 1, 5, and 20 mg/kg or 20 mg/kg intradermally produced no pathological evidence of toxicity. Conclusion: A dose of 20 mg/kg was identified as the no observed adverse effect level following IV or ID routes of administration of IRDye 800CW

Light Harvesting Schemes for High Efficiency Thin Film Silicon Solar Cells

In Thin Film Silicon (TF-Si) solar cells light harvesting schemes must guarantee an efficient light trapping in the thin absorber layers without decreasing the silicon layers quality and consecutively the p-i-n diodes electrical performance. TF-Si solar cells resilience to the substrate roughness is reported to be possibly improved through optimizations of the cell design and of the silicon deposition processes. By further tailoring the superstrate texture, amorphous silicon / microcrystalline silicon (a-Si:H/mu c-Si:H) tandem solar cells with an initial efficiency up to 13.7 % and a stabilized efficiency up to 11.8 % are demonstrated on single-scale textured superstrates. An alternative approach combining large and smooth features nanoimprinted onto a transparent lacquer with small and sharp textures from as-grown LPCVD ZnO is then shown to have a high potential for further increasing TF-Si devices efficiency. First results demonstrate up to 14.1 % initial efficiency for a TF-Si tandem solar cell