Biology subjects

Shin, A.

Publications and source records attributed to Shin, A..

At least 19 recordsLinked to original sources

bioRxiv2026

Electrodeposited Biocompatible Coatings for 3D Electrodes on Retinal Prostheses

Photovoltaic subretinal prosthesis, PRIMA, provides central vision to patients blinded by age-related macular degeneration, with acuity matching the 100 m pixel size. Further miniaturization requires pillar electrodes to position the stimulating surfaces closer to the inner retinal neurons. While such structures can be electroplated in gold and coated on their tops with SIROF, the exposed gold sidewalls are not biocompatible. Sputtering or atomic layer deposition of protective coatings are unsuitable for selectively passivating the pillar structures without also coating the photosensitive regions and return electrodes of the implant. Here, we present a strategy for biocompatible coating of pillar sidewalls while preserving surrounding implant functionality. The approach combines non-critical photoresist lithography to protect planar return electrodes with electrodeposition of TiO2; or Pt onto gold pillar sidewalls. In-vivo studies demonstrated that both TiO2 and Pt coatings are biocompatible and prevent adverse reactions of the retinal tissue to gold. Since specific capacitance of electroplated TiO2 (25 F/cm2) is much lower than that of Pt (240 F/cm2), the former better limits the current from the side walls and ensures that charge injection occurs predominantly through the pillar tops coated with SIROF (~6 mF/cm2). Electrodeposition, combined with noncritical photolithography provides a scalable wafer-level solution for fabrication of biocompatible three-dimensional electro-neural interfaces, addressing a critical bottleneck in bioelectronics.

bioengineering↗

bioRxiv2026

Modeling and validation of parallel co-flows layer widths in open-capillary trigger valve systems

Control of fluids is a hallmark of microfluidic systems and fundamental for the successful application of microfluidic devices. Trigger valves use geometric features to autonomously control the release of fluids in microfluidic devices. Our previous work has adapted geometries used in closed trigger valve systems to enable use in open systems, allowing for open microfluidic devices with up to three trigger valves. Here, we focus on the parallel co-flows produced by sequential release of trigger valves and present a model that predicts their layer widths as a function of the geometric characteristics of the different side channels of each trigger valve. We show layered co-flows with widths as low as 50 microns. Additionally, we expand the use of trigger valves in open microfluidic devices by incorporating 1) varied step heights, 2) devices with up to seven trigger valves, and 3) use of varied fluids and plastics. To validate the implementation and use of these trigger valves in open systems, we have developed a theoretical framework to compare predicted outcomes (i.e., fluid travel distance, velocity, and layering width) with our experimental values. This theoretical work offers applications in various fields, including hydrogel patterning for 3D cell culture, organ-on-a-chip models, at-home sample preparation, and autonomous microfluidic systems for biosensing.

bioengineering↗

bioRxiv2026

From Fabrication to Flow: Impact of Print Orientation on Surface Qualities and Capillary-Driven Flow in Laser SLA-based Open Microchannels

Stereolithography (SLA) 3D printing has become increasingly popular for fabricating microfluidic devices, with applications including hydrogel patterning and tissue modeling. In open-channel systems with surface tension-driven flow, 3D-printer-induced discrepancies in channel surface texture can significantly impact fluid flow and device performance. While previous work has focused on comparing different 3D printing methods for microchannel fabrication, the effect of device orientation during SLA printing on microchannel morphology and capillary-driven flow has not been systematically evaluated. Furthermore, there is minimal research elucidating the influence of channel surface texture on the flow of biologically relevant hydrogel precursors commonly used in organ-on-a-chip applications. Herein, we investigated the impact of print orientation on channel morphology, fluid wetting behavior, and fluid flow by comparing laser SLA-based parts where the length of the channel was tilted at 0{degrees}, 15{degrees}, 45{degrees}, or 90{degrees} during printing. We demonstrated that channel floor surface texture is greatly affected by print orientation: the highest axial surface roughness was measured in 15{degrees} printed channels, and the highest axial surface tortuosity-which describes the real length along the surface-was measured in 45{degrees} printed channels. Print angles of 15{degrees} and 45{degrees} also resulted in asymmetric roughness of the channel floor, which caused asymmetric wetting of glycerol solution. Surface tension-driven flow of glycerol solution, agarose precursor solution, and collagen precursor solution was affected by print orientation, in which the 45{degrees} printed flow devices had slowest flow for all test fluids. Root mean square roughness was not a reliable predictor of slower flow; instead, surface tortuosity should be considered. Potential alternatives to better theoretically model how print angle-induced surface texture affects open-channel flow are discussed as well. These findings provide a framework of fabrication considerations for laser SLA printing of open microchannels that can also be applied to other layer-by-layer, vat photopolymerization-based 3D printing technologies.

bioengineering↗

bioRxiv2026

Accurate strand-specific long-read transcript isoform discovery and quantification at bulk, single-cell, and single-nucleus resolution

Recent advances in long-read transcriptome sequencing enable high-throughput profiling of full-length RNA isoforms in bulk, single-cell, and single-nucleus samples. However, long-read datasets typically contain a mixture of complete and partial transcripts, leading to pervasive ambiguity in read-to-isoform assignment and complicating accurate isoform identification and quantification, particularly in the absence of reliable reference annotations. These challenges are further amplified in single-cell and single-nucleus samples, where coverage is sparse and transcriptional heterogeneity is high. Here, we present the Long Read Alignment Assembler (LRAA), a unified and versatile computational framework for isoform identification and quantification from long-read RNA sequencing data across bulk, single-cell, and single-nucleus transcriptomic samples. LRAA combines splice-graph based structural modeling with expectation maximization based optimization to probabilistically resolve ambiguous read assignments and improve isoform abundance estimation. The framework supports quantification-only, reference-guided, and fully reference-free (de novo) modes of analysis within a single methodological paradigm. We benchmarked LRAA using both simulated and genuine long-read datasets spanning sequencing standards and whole transcriptomes. Central to this evaluation is a novel benchmarking strategy based on Multiplexed Overexpression of Regulatory Factors (MORFs), which provides biologically expressed, barcoded isoforms with unambiguous read-level ground truth. Across all benchmarks, including MORFs, synthetic spike-ins, and whole-transcriptome datasets, LRAA consistently outperformed state-of-the-art methods in isoform identification accuracy, sensitivity, and expression quantification. Finally, we demonstrate the biological utility of LRAA by resolving cell-type-specific isoform usage across peripheral blood immune cell populations and by detecting a pathogenic cryptic isoform of STMN2 with associated transcriptional changes in single-nucleus RNA-seq data from frontal cortex tissue of an individual with frontotemporal dementia (FTD). Together, these results establish LRAA as a robust and general solution for resolving transcript diversity in complex biological systems, from development to disease.

bioinformatics↗

bioRxiv2025

Single-Cell RNA Sequencing and Inferred Protein Activity Analysis Reveal a Distinct Tumor Phenotype in Early-Onset Colorectal Cancer Patients

Colorectal cancer (CRC) diagnosed before age 50 years (early-onset CRC, EO-CRC) is rising at an alarming rate, yet its molecular and microenvironmental drivers remain poorly understood. EO-CRC is highly heterogeneous, and while subtle differences from late-onset CRC (LO-CRC) have been reported, their full extent remains unresolved due to the limited scope of previous studies. Here, we integrate public data with in-house clinical samples profiled by single-cell RNA sequencing (scRNA-seq) and multiplex immunofluorescence (mIF) to compare EO-CRC and LO-CRC. Additionally, we employ gene regulatory network-based protein activity inference (VIPER), enabling a more precise characterization of key regulatory proteins driving tumor-stroma interactions. Our analysis reveals that EO-CRC and LO-CRC have a largely similar immune composition, challenging previous reports of an "immune-cold" phenotype in EO-CRC. However, we identify distinct stromal differences, including a significant enrichment of fibroblasts in EO-CRC. Notably, we define a previously unrecognized epithelial subpopulation in EO-CRC, marked by high expression of toll-like receptor 4 (TLR4) and C-C chemokine receptor type 5 (CCR5)--key mediators of inflammation-driven tumor progression and fibroblast recruitment. These findings suggest that EO-CRC may be driven by a tumor-intrinsic inflammatory phenotype with enhanced stromagenesis, providing new insights into potential mechanisms underlying its increasing incidence in young adults.

cancer biology↗

bioRxiv2025

Amorphous silicon resistors enable smaller pixels in photovoltaic retinal prosthesis

ObjectiveClinical trials of the photovoltaic subretinal prosthesis PRIMA demonstrated feasibility of prosthetic central vision with resolution matching its 100{micro}m pixel size. To improve prosthetic acuity further, pixel size should be decreased. However, there are multiple challenges, one of which is related to accommodating a compact shunt resistor within each pixel that discharges the electrodes between stimulation pulses and helps increase the contrast of the electric field pattern. Unfortunately, standard materials used in integrated circuit resistors do not match the resistivity required for small photovoltaic pixels. Therefore, we used a novel material - doped amorphous silicon (a-Si) and integrated it into photovoltaic arrays with pixel sizes down to 20{micro}m. ApproachTo fit within a few {micro}m2 area of the pixels and provide resistance in the M{Omega} range, the material should have sheet resistance of a few hundred k{Omega}/sq, which translates to resistivity of a few {Omega}*cm. The a-Si layer was deposited by low-pressure chemical vapor deposition (LPCVD) and its resistivity was adjusted by PH3 doping before encapsulating the resistors between SiO2 and SiC for stability in-vivo. Main ResultsHigh-resolution retinal implants with integrated shunt resistors were fabricated with values ranging from 0.75 to 4 M{Omega} on top of the photovoltaic pixels of 55, 40, 30 and 20 {micro}m in size. Photoresponsivity with all pixel sizes was approximately 0.53 A/W, as high as in the arrays with no shunt resistor. The shunts shortened electrodes discharge time, with the average electric potential in electrolyte decreasing by only 21-31% when repetition rate increased from 2 to 30 Hz, as opposed to a 54-55% decrease without a shunt. Similarly, contrast of a Landolt C pattern increased from 16-22% with no shunt to 22-34% with a shunt. Further improvement in contrast is expected with pillar electrodes and local returns within each pixel. SignificanceMiniature shunt resistors in a MOhm range can be fabricated from doped a-Si in a process compatible with manufacturing of photovoltaic arrays. The shunt resistors improved current injection and spatial contrast at video frame rates, without compromising the photoresponsivity. These advances are critical for scaling pixel sizes below 100 {micro}m to improve visual acuity of prosthetic vision.

neuroscience↗

bioRxiv2025

Multi-platform evaluation and optimization of single-cell RNA isoform sequencing

Long-read transcriptomics enables isoform identification and quantification at single-cell resolution, but analysis is complicated by artifacts introduced during library preparation. We characterize the distinct artifact profiles of three popular single-cell platforms and demonstrate their impact on isoform identification. We introduce a new method for the identification of a wide range of artifacts in cDNA libraries and novel biochemical and bioinformatic strategies to significantly reduce their impact on downstream applications. Finally, we provide a comprehensive framework for RNA isoform sequencing analysis and interpretation as the field continues to develop.

genetics↗

bioRxiv2025

Detection of inertial effects in capillary flows in open and closed channels

The Lucas-Washburn-Rideal law is commonly applied to describe capillary flow dynamics in closed or open channels, microporous media, such as paper pads and fiber threads or even granulous soil. It assumes a viscous flow regime where capillary forces are counteracted by friction with the solid structure, a valid assumption given the small flow velocities and device dimensions. However, scenarios exist outside the viscous regime, where inertial effects become significant, meaning capillary and friction forces do not fully balance. One well-documented case is the transient inertial regime at the onset of capillary motion. With the advancement of capillary devices, other configurations also raise the possibility of inertia influencing flow behavior. This study introduces a criterion to identify inertial contributions in capillary-driven flows in spatially varying geometries within open or closed channels and demonstrates how the Bosanquet equation can account for inertial effects in rectangular open-channel configurations.

bioengineering↗

bioRxiv2024

CandyCollect: An Open-Microfluidic Device for the Direct Capture and Enumeration of Salivary-Extracellular Vesicles

Extracellular vesicles (EVs) are promising biomarkers for disease detection using a liquid biopsy approach, in which they are enriched and analyzed directly from biofluids. However, implementing EV biomarker technologies in the clinic remains limited by the need for practical and patient-centric biofluid collection methods that are compatible with downstream EV processing and analysis. While saliva offers a non-invasive source of EVs, its complexity and heterogeneity--cells, debris, and other non-EV proteins--can present hurdles when using traditional analytical platforms. Here, we present the CandyCollect, a lollipop-inspired sampling device with open microfluidic channels, as a patient-friendly approach for rapid salivary EV capture. CandyCollect simplifies sample preparation by effectively pre-concentrating EVs in oxygen-plasma treated open microfluidic channels. In this proof-of-principle study, we show that following a 3-5 minute-oral sampling period, EVs collected by the CandyCollect can be released with high purity within minutes and subsequently quantified and analyzed for cargo content. We observed consistent EV capture across repeated collections within individuals and expected variability across healthy participants. Additionally, single and pooled collections of EVs from a healthy participant resulted in a concordant protein profile. Overall, the CandyCollect is a new platform for rapid, non-invasive salivary EV collection and analysis for clinical diagnostics.

bioengineering↗

bioRxiv2024

The dynamics of capillary flow in an open-channel system featuring trigger valves

Trigger valves are fundamental features in capillary-driven microfluidic systems that stop fluid at an abrupt geometric expansion and release fluid when there is flow in an orthogonal channel connected to the valve. The concept was originally demonstrated in closed-channel capillary circuits. We show here that trigger valves can be successfully implemented in open channels. We also show that a series of open-channel trigger valves can be placed alongside or opposite a main channel resulting in a layered capillary flow. We developed a closed form model for the dynamics of the flow at trigger valves based on the concept of average friction length and successfully validated the model against experiments. For the main channel, we discuss layered flow behavior in the light of the Taylor-Aris dispersion theory and in the channel turns by considering Dean theory of mixing. This work has potential applications in autonomous microfluidics systems for biosensing, at-home or point-of-care sample preparation devices, hydrogel patterning for 3D cell culture and organ-on-a-chip models.

bioengineering↗

bioRxiv2024

Experimental and Computational Methods for Allelic Imbalance Analysis from Single-Nucleus RNA-seq Data

Single-cell RNA-seq (scRNA-seq) is emerging as a powerful tool for understanding gene function across diverse cells. Recently, this has included the use of allele-specific expression (ASE) analysis to better understand how variation in the human genome affects RNA expression at the single-cell level. We reasoned that because intronic reads are more prevalent in single-nucleus RNA-Seq (snRNA-Seq), and introns are under lower purifying selection and thus enriched for genetic variants, that snRNA-seq should facilitate single-cell analysis of ASE. Here we demonstrate how experimental and computational choices can improve the results of allelic imbalance analysis. We explore how experimental choices, such as RNA source, read length, sequencing depth, genotyping, etc., impact the power of ASE-based methods. We developed a new suite of computational tools to process and analyze scRNA-seq and snRNA-seq for ASE. As hypothesized, we extracted more ASE information from reads in intronic regions than those in exonic regions and show how read length can be set to increase power. Additionally, hybrid selection improved our power to detect allelic imbalance in genes of interest. We also explored methods to recover allele-specific isoform expression levels from both long- and short-read snRNA-seq. To further investigate ASE in the context of human disease, we applied our methods to a Parkinsons disease cohort of 94 individuals and show that ASE analysis had more power than eQTL analysis to identify significant SNP/gene pairs in our direct comparison of the two methods. Overall, we provide an end-to-end experimental and computational approach for future studies.

genomics↗

bioRxiv2024

Enhancing Prosthetic Vision by Upgrade of a Subretinal Photovoltaic Implant in situ

In patients with atrophic age-related macular degeneration, subretinal photovoltaic implant (PRIMA) provided visual acuity up to 20/440, matching its 100m pixels size. Next-generation implants with smaller pixels should significantly improve the acuity. This study in rats evaluates removal of a subretinal implant, replacement with a newer device, and the resulting grating acuity in-vivo. Six weeks after the initial implantation with planar and 3-dimensional devices, the retina was re-detached, and the devices were successfully removed. Histology demonstrated a preserved inner nuclear layer. Re-implantation of new devices into the same location demonstrated retinal re-attachment to a new implant. New devices with 22m pixels increased the grating acuity from the 100m capability of PRIMA implants to 28m, reaching the limit of natural resolution in rats. Reimplanted devices exhibited the same stimulation threshold as for the first implantation of the same implants in a control group. This study demonstrates the feasibility of safely upgrading the subretinal photovoltaic implants to improve prosthetic visual acuity.

neuroscience↗

bioRxiv2024

CTAT-LR-fusion: accurate fusion transcript identification from long and short read isoform sequencing at bulk or single cell resolution

Gene fusions are found as cancer drivers in diverse adult and pediatric cancers. Accurate detection of fusion transcripts is essential in cancer clinical diagnostics, prognostics, and for guiding therapeutic development. Most currently available methods for fusion transcript detection are compatible with Illumina RNA-seq involving highly accurate short read sequences. Recent advances in long read isoform sequencing enable the detection of fusion transcripts at unprecedented resolution in bulk and single cell samples. Here we developed a new computational tool CTAT-LR-fusion to detect fusion transcripts from long read RNA-seq with or without companion short reads, with applications to bulk or single cell transcriptomes. We demonstrate that CTAT-LR-fusion exceeds fusion detection accuracy of alternative methods as benchmarked with simulated and real long read RNA-seq. Using short and long read RNA-seq, we further apply CTAT-LR-fusion to bulk transcriptomes of nine tumor cell lines, and to tumor single cells derived from a melanoma sample and three metastatic high grade serous ovarian carcinoma samples. In both bulk and in single cell RNA-seq, long isoform reads yielded higher sensitivity for fusion detection than short reads with notable exceptions. By combining short and long reads in CTAT-LR-fusion, we are able to further maximize detection of fusion splicing isoforms and fusion-expressing tumor cells. CTAT-LR-fusion is available at https://github.com/TrinityCTAT/CTAT-LR-fusion/wiki.

cancer biology↗

bioRxiv2023

Three-dimensional electro-neural interfaces electroplated on subretinal prostheses

ObjectiveHigh-resolution retinal prosthetics offer partial restoration of sight to patients blinded by retinal degenerative diseases through electrical stimulation of the remaining neurons. Decreasing the pixel size enables an increase in prosthetic visual acuity, as demonstrated in animal models of retinal degeneration. However, scaling down the size of planar pixels is limited by the reduced penetration depth of the electric field in tissue. We investigate 3-dimensional structures on top of the photovoltaic arrays for enhanced penetration of electric field to permit higher-resolution implants. ApproachWe developed 3D COMSOL models of subretinal photovoltaic arrays that accurately quantify the device electrodynamics during stimulation and verified it experimentally through comparison with the standard (flat) photovoltaic arrays. The models were then applied to optimise the design of 3D electrode structures (pillars and honeycombs) to efficiently stimulate the inner retinal neurons. The return electrodes elevated on top of the honeycomb walls surrounding each pixel orient the electric field inside the cavities vertically, aligning it with bipolar cells for optimal stimulation. Alternatively, pillars elevate the active electrode into the inner nuclear layer, improving proximity to the target neurons. Modelling results informed a microfabrication process of electroplating the 3D electrode structures on top of the existing flat subretinal prosthesis. Main resultsSimulations demonstrate that despite the conductive sidewalls of the 3D electrodes being exposed to electrolyte, most of the charge flows via the high-capacitance sputtered Iridium Oxide film that caps the top of the 3D structures. The 24 {micro}m height of the electroplated honeycomb structures was optimised for integration with the inner nuclear layer cells in rat retina, while 35 {micro}m height of the pillars was optimized for penetrating the debris layer in human patients. Release from the wafer and implantation of the 3D arrays demonstrated that they are mechanically robust to withstand the associated forces. Histology demonstrated successful integration of the 3D structures with the rat retina in-vivo. SignificanceElectroplated 3D honeycomb structures produce a vertically oriented electric field that offers low stimulation threshold, high spatial resolution and high contrast for the retinal implants with pixel sizes down to 20{micro}m in width. Pillar electrodes offer an alternative configuration for extending the stimulation past the debris layers. Electroplating of the 3D structures is compatible with the fabrication process of the flat photovoltaic arrays, thereby enabling much more efficient stimulation than in their original flat configuration.

neuroscience↗

bioRxiv2023

CZ CELLxGENE Discover: A single-cell data platform for scalable exploration, analysis and modeling of aggregated data

Hundreds of millions of single cells have been analyzed to date using high throughput transcriptomic methods, thanks to technological advances driving the increasingly rapid generation of single-cell data. This provides an exciting opportunity for unlocking new insights into health and disease, made possible by meta-analysis that span diverse datasets building on recent advances in large language models and other machine learning approaches. Despite the promise of these and emerging analytical tools for analyzing large amounts of data, a major challenge remains the sheer number of datasets and inconsistent format, data models and accessibility. Many datasets are available via unique portals platforms that often lack interoperability. Here, we present CZ CellxGene Discover (cellxgene.cziscience.com), a data platform that provides curated and interoperable data. This single-cell data resource, available via a free-to-use online data portal, hosts a growing corpus of community contributed data that spans more than 50 million unique cells. Curated, standardized, and associated with consistent cell-level metadata, this collection of interoperable single-cell transcriptomic data is the largest of its kind. A suite of tools and features enables accessibility and reusability of the data via both computational and visual interfaces to allow researchers to rapidly explore individual datasets and perform cross-corpus analysis. This functionality is enabling meta-analyses of tens of millions of cells across studies and tissues and providing global views of human cells at the resolution of single cells.

cell biology↗

bioRxiv2023

3D electronic implants in subretinal space: long-term follow-up in rodents

Photovoltaic subretinal prosthesis (PRIMA) enables restoration of sight via electrical stimulation of the interneurons in degenerated retina, with resolution limited by the 100 m pixel size. Since decreasing the pixel size below 75 m in the current bipolar geometry is impossible, we explore the possibility of using smaller pixels based on a novel 3-dimensional honeycomb-shaped design. We assessed the long-term biocompatibility and stability of these arrays in rats by investigating the anatomical integration of the retina with flat and 3D implants and response to electrical stimulation over lifetime - up to 9 months post-implantation in aged rats. With both flat and 3D implants, VEP amplitude decreased after the day of implantation by more than 3-fold, and gradually recovered over about 3 months. With 25 m high honeycomb walls, the majority of bipolar cells migrate into the wells, while amacrine and ganglion cells remain above the cavities, which is essential for selective network-mediated stimulation of the second-order neurons. Retinal thickness and full-field stimulation threshold with 40 m-wide honeycomb pixels were comparable to those with planar devices - 0.05 mW/mm2 with 10ms pulses. However, fewer cells from the inner nuclear layer migrated into the 20 m-wide wells, and stimulation threshold increased over 5 months, before stabilizing at about 0.08 mW/mm2. Such threshold is significantly lower than 1.8 mW/mm2 with a previous design of flat bipolar pixels, confirming the promise of the 3D honeycomb-based approach to high resolution subretinal prosthesis.

neuroscience↗

bioRxiv2023

APOE4/4 is linked to damaging lipid droplets in Alzheimer's microglia

Several genetic risk factors for Alzheimers Disease (AD) implicate genes involved in lipid metabolism and many of these lipid genes are highly expressed in glial cells. However, the relationship between lipid metabolism in glia and AD pathology remains poorly understood. Through single-nucleus RNA-sequencing of AD brain tissue, we have identified a microglial state defined by the expression of the lipid droplet (LD) associated enzyme ACSL1 with ACSL1-positive microglia most abundant in AD patients with the APOE4/4 genotype. In human iPSC-derived microglia (iMG) fibrillar A{beta} (fA{beta}) induces ACSL1 expression, triglyceride synthesis, and LD accumulation in an APOE-dependent manner. Additionally, conditioned media from LD-containing microglia leads to Tau phosphorylation and neurotoxicity in an APOE-dependent manner. Our findings suggest a link between genetic risk factors for AD with microglial LD accumulation and neurotoxic microglial-derived factors, potentially providing novel therapeutic strategies for AD.

neuroscience↗

bioRxiv2022

Cellular integration with a subretinal honeycomb-shaped prosthesis

In patients blinded by geographic atrophy, subretinal photovoltaic implant with 100{micro}m pixels provided visual acuity closely matching the pixel pitch. However, such flat bipolar pixels cannot be scaled below 75{micro}m, limiting the attainable visual acuity. This limitation can be overcome by shaping the electric field with 3-dimensional electrodes. In particular, elevating the return electrode on top of honeycomb-shaped vertical walls surrounding each pixel extends the electric field vertically and decouples its penetration into tissue from the pixel width. This approach relies on migration of the retinal cells into the honeycomb wells. Here, we demonstrate that the majority of the inner retinal neurons migrate into 25{micro}m deep wells, leaving the third-order neurons, such as amacrine and ganglion cells, outside. This is important for selective stimulation of the second-order neurons to preserve the retinal signal processing in prosthetic vision. Comparable glial response to that with flat implants suggests that migration and separation of the retinal cells by the walls does not cause additional stress. Furthermore, retinal migration into the honeycombs does not negatively affect its electrical excitability.

neuroscience↗