Solid-State Nanopores for Spatially Resolved Chemical Neuromodulation.

Most neural prosthetic devices are based on electrical stimulation, although the modulation of neuronal activity by a localized chemical delivery would better mimic physiological synaptic machinery. In the past decade, various drug delivery approaches attempted to emulate synaptic transmission, although they were hampered by poor retention of their cargo while reaching the target destination, low spatial resolution, and poor biocompatibility and stability of the materials involved. Here, we propose a planar solid-state device for multisite neurotransmitter translocation at the nanoscale consisting of a nanopatterned ceramic membrane connected to a reservoir designed to store neurotransmitters.

The Progression of Stargardt Disease as Determined by Spectral-Domain Optical Coherence Tomography over a 24-Month Period (ProgStar Report No. 18).

Introduction: The aim of this study was to evaluate the progression of atrophy as determined by spectral-domain optical coherence tomography (SD-OCT) in patients with molecularly confirmed ABCA4-associated Stargardt disease type 1 (STGD1) over a 24-month period in a multicenter prospective cohort study.

Methods: SD-OCT images from 428 eyes of 236 patients were analyzed. Change of mean thickness (MT) and intact area were estimated after semiautomated segmentation for the following individual layers in the central subfield (CS), inner ring (IR), and outer ring (OR) of the ETDRS grid: retinal pigment epithelium (RPE), outer segments (OSs), inner segments (IS), outer nuclear layer (ONL) inner retina (IR), and total retina.

Effects of Miosis on the Visual Acuity Space under Varying Conditions of Contrast and Ambient Luminance in Presbyopia.

Presbyopia is an age-related ocular condition, typically affecting individuals aged over 40 years, characterized by a gradual and irreversible decline in the eye's ability to focus on nearby objects. Correction methods for presbyopia encompass the use of corrective lenses, surgical interventions (corneal or lens based), and, more recently, the FDA-approved topical administration of 1.25% pilocarpine.

Sustained Extracellular Electrical Stimulation Modulates the Permeability of Gap Junctions in Mouse Retina with Photoreceptor Degeneration.

Neurons build vast gap junction-coupled networks (GJ-nets) that are permeable to ions or small molecules, enabling lateral signaling. Herein, we investigate (1) the effect of blinding diseases on GJ-nets in mouse retinas and (2) the impact of electrical stimulation on GJ permeability. GJ permeability was traced in the acute retinal explants of blind retinal degeneration 1 () mice using the GJ tracer neurobiotin.

Improvements for recording retinal function with Microelectrode Arrays.

A microelectrode array (MEA) is a configuration of multiple electrodes that enables the concurrent targeting of multiple sites for extracellular recording and stimulation. By utilizing light pulses or electrical stimulations, MEA recordings unveil the complex patterns of electrical activities that arise from the signaling processes within the retinal network. Here, we present a stepwise approach for using microelectrode arrays (MEAs) for recording action potentials from the mouse retina in response to electrical and light stimuli.

Electrical Input Filters of Ganglion Cells in Wild Type and Degenerating rd10 Mouse Retina as a Template for Selective Electrical Stimulation.

Bionic vision systems are currently limited by indiscriminate activation of all retinal ganglion cells (RGCs)- despite the dozens of known RGC types which each encode a different visual message. Here, we use spike-triggered averaging to explore how electrical responsiveness varies across RGC types toward the goal of using this variation to create type-selective electrical stimuli. A battery of visual stimuli and a randomly distributed sequence of electrical pulses were delivered to healthy and degenerating (4-week-old rd10) mouse retinas.

Artificial Vision: The High-Frequency Electrical Stimulation of the Blind Mouse Retina Decay Spike Generation and Electrogenically Clamped Intracellular Ca at Elevated Levels.

Background: The electrical stimulation (stim) of retinal neurons enables blind patients to experience limited artificial vision. A rapid response outage of the stimulated ganglion cells (GCs) allows for a low visual sensation rate. Hence, to elucidate the underlying mechanism, we investigated different stim parameters and the role of the neuromodulator calcium (Ca).

Using Micro-Electrode-Array Recordings and Retinal Disease Models to Elucidate Visual Functions: Simultaneous Recording of Local Electroretinograms and Ganglion Cell Action Potentials Reveals the Origin of Retinal Oscillatory Potentials.

Background: The electroretinogram (ERG) is an essential diagnostic tool for visual function, both in clinical and research settings. Here, we establish an advanced in vitro approach to assess cell-type-specific ERG signal components.

Methods: Retinal explant cultures, maintained under entirely controlled conditions, were derived from wild-type mice and and cone-degeneration mouse models.

The VA-CAL Test Quantifies Improvement of Visual Acuity in Achromatopsia by Means of Short-Wave Cutoff Filter Glasses in Daily Living Conditions.

Purpose: To quantify visual performance of patients with achromatopsia at various contrast and luminance combinations typical for daily living conditions, in comparison to controls, and to measure beneficial effects of short-wavelength cutoff filter glasses used by patients with achromatopsia to reduce glare sensation.

Methods: Best-corrected visual acuity (BCVA) was tested with Landolt rings using an automated device (VA-CAL test). The visual acuity space was assessed for each participant with and without filter glasses (transmission >550 nm) at 46 contrast-luminance combinations (18%-95%; 0-10,000 cd/m2).

Monocular transcorneal electrical stimulation induces ciliary muscle thickening in contralateral eye.

Transcorneal electrical stimulation (TES) is used as therapy for retinal diseases such as retinitis pigmentosa (RP) and was suggested for assessing retinal sensitivity by determining phosphene thresholds, subjective luminance impressions caused by retinal stimulation. Further applications concerned the accommodation process, revealing an improved accommodative amplitude in presbyopic eyes after TES treatment. The respective changes of the ciliary muscle (CM), the structure most important for near vision, during TES are yet unknown.

Elaborate Evaluation of Farnsworth Dichotomous D-15 Panel Test Can Help Differentiate between Best Vitelliform Macular Dystrophy and Autosomal Recessive Bestrophinopathy.

Introduction: The colour vision in bestrophinopathies has not been assessed in detail so far. The aim of this study was to explore the extent to which distinct types of bestrophinopathies differ in regard to colour vision deficiencies using Farnsworth Dichotomous D-15 and Lanthony Desaturated D-15 panel tests.

Methods: Both D-15 tests were performed in 52 eyes of 26 patients with Best vitelliform macular dystrophy (BVMD) and 10 eyes of 5 patients with autosomal recessive bestrophinopathy (ARB).

Nature-inspired saccadic-like electrical stimulation paradigm promotes sustained retinal ganglion cell responses by spatiotemporally alternating activation of contiguous multi-electrode patterns.

. Retinal electrical stimulation using multi-electrode arrays (MEAs) aims to restore visual object perception in blind patients. However, the rate and duration of the artificial visual sensations are limited due to the rapid response decay of the stimulated neurons.

Ophthalmic and Genetic Features of Bardet Biedl Syndrome in a German Cohort.

The aim of this study was to characterize the ophthalmic and genetic features of Bardet Biedl (BBS) syndrome in a cohort of patients from a German specialized ophthalmic care center. Sixty-one patients, aged 5−56 years, underwent a detailed ophthalmic examination including visual acuity and color vision testing, electroretinography (ERG), visually evoked potential recording (VEP), fundus examination, and spectral domain optical coherence tomography (SD-OCT). Adaptive optics flood illumination ophthalmoscopy was performed in five patients.

Classification of pseudocalcium visual responses from mouse retinal ganglion cells.

Recently, a detailed catalog of 32 retinal ganglion cell (RGC) visual response patterns in mouse has emerged. However, the 10,000 samples required for this catalog-based on fluorescent signals from a calcium indicator dye-are much harder to acquire from the extracellular spike train recordings underlying our bionic vision research. Therefore, we sought to convert spike trains into pseudocalcium signals so that our data could be directly matched to the 32 predefined, calcium signal-based groups.

Central Visual Function and Genotype-Phenotype Correlations in PDE6A-Associated Retinitis Pigmentosa.

Purpose: Autosomal recessive retinitis pigmentosa (arRP) can be caused by mutations in the phosphodiesterase 6A (PDE6A) gene. Here, we describe the natural course of disease progression with respect to central retinal function (i.e.

Quantification of the Dynamic Visual Acuity Space at Real-World Luminances and Contrasts: The VA-CAL Test.

Purpose: Best-corrected visual acuity (BCVA) is assessed at a single standardized luminance with maximum optotype contrast, not reflecting the constantly changing daily-life viewing conditions. For a more realistic estimation of visual performance at varying object contrasts (Cs) and ambient luminances (ALs), we developed a new VA test, VA-CAL.

Methods: Landolt-C-rings between 18% and 95% Weber contrast, were presented at 1 m distance (8 Alternative Forced Choice) on a 5.

Bioengineering strategies for restoring vision.

Late-stage retinal degenerative disease involving photoreceptor loss can be treated by optogenetic therapy, cell transplantation and retinal prostheses. These approaches aim to restore light sensitivity to the retina as well as visual perception by integrating neuronal responses for transmission to the cortex. In age-related macular degeneration, some cell-based therapies also aim to restore photoreceptor-supporting tissue to prevent complete photoreceptor loss.

Three-Year Changes in Visual Function in the Placebo Group of a Randomized Double-Blind International Multicenter Safety Study: Analysis of Electroretinography, Perimetry, Color Vision, and Visual Acuity in Individuals With Chronic Stable Angina Pectoris.

Purpose: To determine whether significant deteriorations in objective (electroretinography [ERG]) and subjective (standard automated and semi-automated kinetic perimetry; color discrimination; and best-corrected visual acuity) tests of visual function, potentially attributable to aging, occurred in the group randomized to placebo of a 3-year prospective multicenter ocular safety study of ivabradine for chronic stable angina pectoris.

Methods: The multicenter trial was conducted at 11 international ophthalmic centers. Changes in visual function between baseline and month 36 were analyzed by means of a two-tailed Wilcoxon signed-rank test, based on the Hodges and Lehman estimator of the median difference, with the 95% confidence intervals derived by Walsh averages.

Oscillatory Potentials in Achromatopsia as a Tool for Understanding Cone Retinal Functions.

Achromatopsia (ACHM) is an inherited autosomal recessive disease lacking cone photoreceptors functions. In this study, we characterize the time-frequency representation of the full-field electroretinogram (ffERG) component oscillatory potentials (OPs), to investigate the connections between photoreceptors and the inner retinal network using ACHM as a model. Time-frequency characterization of OPs was extracted from 52 controls and 41 achromat individuals.