Optogenetic vision restoration in the face of secondary and tertiary remodeling in the rd1 mouse retina.

Photoreceptor loss in retinal degeneration is followed by progressive remodeling of the surviving retina, which may present a barrier to vision restoration. To determine the impact of remodeling on the retina's suitability for therapeutic interventions, we track changes in visual code produced by the optogenetic actuator ReaChR expressed in ON-bipolar cells of the rd1 mouse at 3, 5, 9, and 12 months. Anatomical analyses confirm that these ages encompass phase II (photoreceptor degeneration) to phase III (inner retinal thinning, dysmorphia, pigment epithelium infiltration) remodeling.

The intersection of obesity and acute heart failure: Cardiac structure and function and congestion across BMI categories.

Background: Overweight/obesity are important risk factors for heart failure (HF), however, the pathophysiologic consequences of obesity in patients with acute HF (AHF) are incompletely understood.

Methods: We examined cardiac structure and function, and congestion-related markers in adults hospitalized for AHF across 3 body mass index (BMI) groups: 18.5-24.

Interaction between native and prosthetic visual responses in optogenetic visual restoration.

Degenerative retinal disorders leading to irreversible photoreceptor death are a common cause of blindness. Optogenetic gene therapy aims to restore vision in affected individuals by introducing light-sensitive opsins into the surviving neurons of the inner retina. While up until now, the main focus of optogenetic therapy has been on terminally blind individuals, treating at stages where residual native vision is present could have several advantages.

The ERGtools2 package: a toolset for processing and analysing visual electrophysiology data.

Purpose: To introduce ERGtools2, an open-source R package for processing, analysing and long-term storing visual electrophysiology data.

Methods: A dataset comprising Electroretinogram (ERG) recordings of C57Bl/6J mice, subjected to standard ISCEV stimuli, was used to present the functionality of ERGtools2. ERGtools2 stores and organizes all recordings, metadata, and measurement information from an individual examination in a single object, maintaining raw data throughout the analysis process.

Expression of Osteopontin in M2 and M4 Intrinsically Photosensitive Retinal Ganglion Cells in the Mouse Retina.

Purpose: Melanopsin-expressing intrinsically photosensitive (ip) retinal ganglion cells (RGCs) can be divided into six different subtypes (M1 - M6). Yet, specific markers exist for only some of these subtypes that could be employed to study the function of individual subtypes. Osteopontin (Spp1) marks αRGC, suggesting that, across ipRGCs, it would only mark the M4-ipRGC subtype (synonymous to ON-sustained αRGCs).

Enhanced restoration of visual code after targeting ON bipolar cells compared with retinal ganglion cells with optogenetic therapy.

Optogenetic therapy is a promising vision restoration method where light-sensitive opsins are introduced to the surviving inner retina following photoreceptor degeneration. The cell type targeted for opsin expression will likely influence the quality of restored vision. However, a like-for-like preclinical comparison of visual responses evoked following equivalent opsin expression in the two major targets, ON bipolar (ON BCs) or retinal ganglion cells (RGCs), is absent.

A versatile functional interaction between electrically silent K subunits and K7 potassium channels.

Voltage-gated K (K) channels govern K ion flux across cell membranes in response to changes in membrane potential. They are formed by the assembly of four subunits, typically from the same family. Electrically silent K channels (KS), however, are unable to conduct currents on their own.

Predictors of heart failure readmission and all-cause mortality in patients with acute heart failure.

Background: Predischarge risk stratification of patients with acute heart failure (AHF) could facilitate tailored treatment and follow-up, however, simple scores to predict short-term risk for HF readmission or death are lacking.

Methods: We sought to develop a congestion-focused risk score using data from a prospective, two-center observational study in adults hospitalized for AHF. Laboratory data were collected on admission.

Association of Lesion Location and Functional Parameters with Vision-Related Quality of Life in Geographic Atrophy Secondary to Age-related Macular Degeneration.

Objective: The primary goal of this study was to determine how structural and functional parameters influence the vision-related quality of life (VRQoL) in patients suffering from geographic atrophy (GA) secondary to age-related macular degeneration.

Design: This study was designed as a prospective, noninterventional, natural-history study (Directional Spread in Geographic-Atrophy study, NCT02051998).

Subjects: The research involved 82 patients with bilateral GA.

Impact of lesion location and functional parameters on vision-related quality of life in geographic atrophy secondary to AMD.

Background/aims: The primary objective was to determine how structural and functional parameters influence the vision-related quality of life (VRQoL) in patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD).

Methods: This prospective, non-interventional, natural-history 'Directional Spread in Geographic-Atrophy' study was conducted at the University Eye Hospital in Bonn, enrolling 82 patients with bilateral GA. Parameters such as GA location (assessed by the Early Treatment Diabetic Retinopathy Study grid), best-corrected visual acuity (BCVA), low-luminance visual acuity (LLVA), reading acuity, and speed were examined.

Left atrial inflow propagation velocity derived by color M-mode Doppler in acute heart failure.

Left atrial (LA) inflow propagation velocity from the pulmonary vein (LAIF-PV) has been proposed as a novel measure of LA reservoir function and is associated with pulmonary capillary wedge pressure in critically ill patients. However, data on LAIF-PV in acute heart failure (AHF) are lacking. We sought to examine the feasibility of measuring LAIF-PV and evaluate clinical and echocardiographic correlates of LAIF-PV in AHF.

Functional integrity of visual coding following advanced photoreceptor degeneration.

Photoreceptor degeneration sufficient to produce severe visual loss often spares the inner retina. This raises hope for vision restoration treatments using optogenetics or electrical stimulation, which generate a replacement light input signal in surviving neurons. The success of these approaches is dependent on the capacity of surviving circuits of the visual system to generate and propagate an appropriate visual code in the face of neuroanatomical remodeling.

Health-related quality of life in acute heart failure: association between patient-reported symptoms and markers of congestion.

Aims: The aim of this study was to examine the association between patient-reported symptoms and the extent of pulmonary congestion in acute heart failure (AHF).

Methods And Results: In this prospective, observational study, patient-reported symptoms were assessed at baseline using the Kansas City Cardiomyopathy Questionnaire total symptom score (KCCQ-TSS) (range 0-100; 0 worst) in patients hospitalized for AHF. In a subset, patient-reported dyspnoea at rest and on exertion was examined (range 0-10; 10 worst) at baseline.

Optogenetics for visual restoration: From proof of principle to translational challenges.

Degenerative retinal disorders are a diverse family of diseases commonly leading to irreversible photoreceptor death, while leaving the inner retina relatively intact. Over recent years, innovative gene replacement therapies aiming to halt the progression of certain inherited retinal disorders have made their way into clinics. By rendering surviving retinal neurons light sensitive optogenetic gene therapy now offers a feasible treatment option that can restore lost vision, even in late disease stages and widely independent of the underlying cause of degeneration.

A systematic comparison of optogenetic approaches to visual restoration.

During inherited retinal degenerations (IRDs), vision is lost due to photoreceptor cell death; however, a range of optogenetic tools have been shown to restore light responses in animal models. Restored response characteristics vary between tools and the neuronal cell population to which they are delivered: the interplay between these is complex, but targeting upstream neurons (such as retinal bipolar cells) may provide functional benefit by retaining intraretinal signal processing. In this study, our aim was to compare two optogenetic tools: mammalian melanopsin (hOPN4) and microbial red-shifted channelrhodopsin (ReaChR) expressed within two subpopulations of surviving cells in a degenerate retina.

Prevalence and prognostic importance of lung ultrasound findings in acute coronary syndrome: A systematic review.

Background: Heart failure (HF) complicating acute coronary syndrome (ACS) is a herald of adverse outcomes. In this systematic review, we investigated the prevalence of lung ultrasound (LUS) findings and their prognostic utility among patients with ACS.

Methods: We searched the online databases PubMed, EMBASE, and Web of Science for studies (full-text articles, published in English) that used LUS in adult patients with ACS [ST-elevation myocardial infarction (STEMI), non-ST-elevation myocardial infarction (NSTEMI), and unstable angina].

Association of Reading Performance in Geographic Atrophy Secondary to Age-Related Macular Degeneration With Visual Function and Structural Biomarkers.

Importance: As a disabling and frequent disease, geographic atrophy secondary to age-related macular degeneration (AMD) constitutes an important study subject. Emerging clinical trials require suitable end points. The characterization and validation of reading performance as a functional outcome parameter is warranted.

Modeling of atrophy size trajectories: variable transformation, prediction and age-of-onset estimation.

Background: To model the progression of geographic atrophy (GA) in patients with age-related macular degeneration (AMD) by building a suitable statistical regression model for GA size measurements obtained from fundus autofluorescence imaging.

Methods: Based on theoretical considerations, we develop a linear mixed-effects model for GA size progression that incorporates covariable-dependent enlargement rates as well as correlations between longitudinally collected GA size measurements. To capture nonlinear progression in a flexible way, we systematically assess Box-Cox transformations with different transformation parameters λ.

[Intrinsically photosensitive retinal ganglion cells].

Background: Melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGC) area third class of photoreceptors in the retina in addition to rods and cones. They are a small heterogeneous population of cells primarily mediating non-image-forming visual functions.

Objective: This article provides an overview of the current understanding of the functions and the diversity of ipRGCs.

Analysis of imaging biomarkers and retinal nerve fiber layer thickness in RPGR-associated retinitis pigmentosa.

Purpose: To investigate multimodal retinal imaging characteristics including the retinal nerve fiber layer (RNFL) thickness in patients with RPGR-associated retinitis pigmentosa (RP).

Methods: This cross-sectional case-control study included 17 consecutive patients (median age, 21 years) with RPGR-associated RP who underwent retinal imaging including optical coherence tomography (OCT), short-wavelength fundus autofluorescence (AF) imaging, and RNFL scans centered on the optic disc. RNFL thickness was manually segmented and compared to clinical and imaging parameters including the transfoveal ellipsoid zone (EZ) width, the horizontal diameter of the macular hyperautofluorescent ring.

A-lines and B-lines in patients with acute heart failure.

Aims: Lung ultrasound (LUS) relies on detecting artefacts, including A-lines and B-lines, when assessing dyspnoeic patients. A-lines are horizontal artefacts and characterize normal lung, whereas multiple vertical B-lines are associated with increased lung density. We sought to assess the prevalence of A-lines and B-lines in patients with acute heart failure (AHF) and examine their clinical correlates and their relationship with outcomes.

ON-bipolar cell gene expression during retinal degeneration: Implications for optogenetic visual restoration.

Purpose: Retinal bipolar cells survive even in the later stages of inherited retinal degenerations (IRDs) and so are attractive targets for optogenetic approaches to vision restoration. However, it is not known to what extent the remodelling that these cells undergo during degeneration affects their function. Specifically, it is unclear if they are free from metabolic stress, receptive to adeno-associated viral vectors, suitable for opsin-based optogenetic tools and able to propagate signals by releasing neurotransmitter.