Novel use of plga microspheres to create an animal model of glaucoma with progressive neuroretinal degeneration

Progressive degeneration of neuroretinal tissue with maintained elevated intraocular pressure (IOP) to simulate chronic glaucoma was produced by intracameral injections of poly (lactic-co-glycolic) acid (PLGA) microspheres (Ms) in rat eyes. The right eye of 39 rats received different sizes of PLGA-Ms (2 µL suspension; 10% w/v): 14 with 38–20 µm Ms (Ms38/20 model) and 25 with 20–10 µm particles (Ms20/10 model). This novel glaucoma animal model was compared to the episcleral vein sclerosis (EPI) model (25 eyes). Injections were performed at baseline, two, four and six weeks. Clinical signs, IOP, retina and optic nerve thicknesses (using in vivo optical coherence tomography; OCT), and histological studies were performed. An IOP increment was observed in all three groups, however, the values obtained from the PLGA-Ms injection resulted lower with a better preservation of the ocular surface. In fact, the injection of Ms20/10 created a gentler, more progressive, and more sustained increase in IOP. This IOP alteration was correlated with a significant decrease in most OCT parameters and in histological ganglion-cell count for the three conditions throughout the eight-week follow-up. In all cases, progressive degeneration of the retina, retinal ganglion cells and optic nerve, simulating chronic glaucoma, was detected by OCT and corroborated by histological study. Results showed an alternative glaucoma model to the well-known episcleral vein model, which was simpler to perform, more reproducible and easier to monitor in vivo

The HADES RV Programme with HARPS-N@TNG II. Data treatment and simulations

The distribution of exoplanets around low-mass stars is still not well understood. Such stars, however, present an excellent opportunity of reaching down to the rocky and habitable planet domains. The number of current detections used for statistical purposes is still quite modest and different surveys, using both photometry and precise radial velocities, are searching for planets around M dwarfs. Our HARPS-N red dwarf exoplanet survey is aimed at the detection of new planets around a sample of 78 selected stars, together with the subsequent characterization of their activity properties. Here we investigate the survey performance and strategy. From 2700 observed spectra, we compare the radial velocity determinations of the HARPS-N DRS pipeline and the HARPS-TERRA code, we calculate the mean activity jitter level, we evaluate the planet detection expectations, and we address the general question of how to define the strategy of spectroscopic surveys in order to be most efficient in the detection of planets. We find that the HARPS-TERRA radial velocities show less scatter and we calculate a mean activity jitter of 2.3 m/s for our sample. For a general radial velocity survey with limited observing time, the number of observations per star is key for the detection efficiency. In the case of an early M-type target sample, we conclude that approximately 50 observations per star with exposure times of 900 s and precisions of about 1 m/s maximizes the number of planet detections

Influence of chronic ocular hypertension on emmetropia: Refractive, structural and functional study in two rat models

Chronic ocular hypertension (OHT) influences on refraction in youth and causes glaucoma in adulthood. However, the origin of the responsible mechanism is unclear. This study analyzes the effect of mild-moderate chronic OHT on refraction and neuroretina (structure and function) in young-adult Long-Evans rats using optical coherence tomography and electroretinography over 24 weeks. Data from 260 eyes were retrospectively analyzed in two cohorts: an ocular normotension (ONT) cohort (20 mmHg), in which OHT was induced either by sclerosing the episcleral veins (ES group) or by injecting microspheres into the anterior chamber. A trend toward emmetropia was found in both cohorts over time, though it was more pronounced in the OHT cohort (p < 0.001), especially in the ES group (p = 0.001) and males. IOP and refraction were negatively correlated at week 24 (p = 0.010). The OHT cohort showed early thickening in outer retinal sectors (p < 0.050) and the retinal nerve fiber layer, which later thinned. Electroretinography demonstrated early supranormal amplitudes and faster latencies that later declined. Chronic OHT accelerates emmetropia in Long–Evans rat eyes towards slowly progressive myopia, with an initial increase in structure and function that reversed over time. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

HADES RV Programme with HARPS-N at TNG VI. GJ 3942 b behind dominant activity signals

Short- to mid-term magnetic phenomena on the stellar surface of M-type stars cannot only resemble the effects of planets in radial velocity data, but also may hide them. We analyze 145 spectroscopic HARPS-N observations of GJ 3942 taken over the past five years and additional photometry to disentangle stellar activity effects from genuine Doppler signals as a result of the orbital motion of the star around the common barycenter with its planet. To achieve this, we use the common methods of pre-whitening, and treat the correlated red noise by a first-order moving average term and by Gaussian-process regression following an MCMC analysis. We identify the rotational period of the star at 16.3 days and discover a new super-Earth, GJ 3942 b, with an orbital period of 6.9 days and a minimum mass of 7.1 Me. An additional signal in the periodogram of the residuals is present but we cannot claim it to be related to a second planet with sufficient significance at this point. If confirmed, such planet candidate would have a minimum mass of 6.3 Me and a period of 10.4 days, which might indicate a 3:2 mean-motion resonance with the inner planet

Chronic glaucoma using biodegradable microspheres to induce intraocular pressure elevation. Six-month follow-up

Background: To compare two prolonged animal models of glaucoma over 24 weeks of follow-up. A novel pre-trabecular model of chronic glaucoma was achieved by injection of biodegradable poly lactic-co-glycolic acid (PLGA) microspheres (10–20 µm) (Ms20/10) into the ocular anterior chamber to progressively increase ocular hypertension (OHT). Methods: Rat right eyes were injected to induce OHT: 50% received a suspension of Ms20/10 in the anterior chamber at 0, 2, 4, 8, 12, 16 and 20 weeks, and the other 50% received a sclerosing episcleral vein injection biweekly (EPIm). Ophthalmological clinical signs, intraocular pressure (IOP), neuroretinal functionality measured by electroretinography (ERG), and structural analysis of the retina, retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) protocols using optical coherence tomography (OCT) and histological exams were performed. Results: Both models showed progressive neuroretinal degeneration (p < 0.05), and contralateral eye affectation. The Ms20/10 model showed a more progressive increase in IOP and better preservation of ocular surface. Although no statistical differences were found between models, the EPIm showed a tendency to produce thicker retinal and thinner GCL thicknesses, slower latency and smaller amplitude as measured using ERG, and more aggressive disturbances in retinal histology. In both models, while the GCL showed the greatest percentage loss of thickness, the RNFL showed the greatest and earliest rate of thickness loss. Conclusions: The intracameral model with biodegradable microspheres resulted more like the conditions observed in humans. It was obtained by a less-aggressive mechanism, which allows for adequate study of the pathology over longer periods. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Variability Timescale and Spectral Index of Sgr A* in the Near Infrared: Approximate Bayesian Computation Analysis of the Variability of the Closest Supermassive Black Hole

Sagittarius A* (Sgr A*) is the variable radio, near-infrared (NIR), and X-ray source associated with accretion onto the Galactic center black hole. We present an analysis of the most comprehensive NIR variability dataset of Sgr A* to date: eight 24-hour epochs of continuous monitoring of Sgr A* at 4.5 $\mu$m with the IRAC instrument on the Spitzer Space Telescope, 93 epochs of 2.18 $\mu$m data from Naos Conica at the Very Large Telescope, and 30 epochs of 2.12 $\mu$m data from the NIRC2 camera at the Keck Observatory, in total 94,929 measurements. A new approximate Bayesian computation method for fitting the first-order structure function extracts information beyond current Fast Fourier Transformation (FFT) methods of power spectral density (PSD) estimation. With a combined fit of the data of all three observatories, the characteristic coherence timescale of Sgr A* is $\tau_{b} = 243^{+82}_{-57}$ minutes ($90\%$ credible interval). The PSD has no detectable features on timescales down to 8.5 minutes ($95\%$ credible level), which is the ISCO orbital frequency for a dimensionless spin parameter $a = 0.92$. One light curve measured simultaneously at 2.12 and 4.5 $\mu$m during a low flux-density phase gave a spectral index $\alpha_s = 1.6 \pm 0.1$ ($F_\nu \propto \nu^{-\alpha_s}$). This value implies that the Sgr A* NIR color becomes bluer during higher flux-density phases. The probability densities of flux densities of the combined datasets are best fit by log-normal distributions. Based on these distributions, the Sgr A* spectral energy distribution is consistent with synchrotron radiation from a non-thermal electron population from below 20 GHz through the NIR.Comment: Accepted for publication in ApJ on May 30, 2018. A machine readable version of the light curve data is included in the journal's online publication. Version 2 includes proof correction