Pre-analytical considerations in the development of a prototype SARS-CoV-2 antigen ARCHITECT automated immunoassay.

OBJECTIVES: To evaluate pre-analytical challenges related to high-volume central laboratory SARS-CoV-2 antigen testing with a prototype qualitative SARS-CoV-2 antigen immunoassay run on the automated Abbott ARCHITECT instrument. METHODS: Contrived positive and negative specimens and de-identified nasal and nasopharyngeal specimens in transport media were used to evaluate specimen and reagent on-board stability, assay analytical performance and interference, and clinical performance. RESULTS: TCID50/mL values were similar for specimens in various transport media. Inactivated positive clinical specimens and viral lysate (USA-WA1/2020) were positive on the prototype immunoassay. Within-laboratory imprecision was ≤0.10 SD (<1.00 S/C) with a ≤10% CV (≥1.00 S/C). Assay reagents were stable on board the instrument for 14 days. No high-dose hook effect was observed with a SARS-CoV-2 stock of Ct 13.0 (RLU>1.0 × 106). No interference was observed from mucin, whole blood, 12 drugs, and more than 20 cross-reactants. While specimen stability was limited at room temperature for specimens with or without viral inactivation, a single freeze/thaw cycle or long-term storage (>30 days) at -20 °C did not adversely impact specimen stability or assay performance. Specificity of the prototype SARS-CoV-2 antigen immunoassay was ≥98.5% and sensitivity was ≥89.5% across two ARCHITECT instruments. Assay sensitivity was inversely correlated with Ct and was similar to that reported for the Roche Elecsys® SARS-CoV-2 Ag immunoassay. CONCLUSIONS: The prototype SARS-CoV-2 antigen ARCHITECT immunoassay is sensitive and specific for detection of SARS-CoV-2 in nasal and nasopharyngeal specimens. Endogenous proteases in mucus may degrade the target antigen, which limits specimen storage and transport times and complicates assay workflow.

Simultaneous Online Registration-Independent Stiffness Identification and Tip Localization of Surgical Instruments in Robot-assisted Eye Surgery.

Notable challenges during retinal surgery lend themselves to robotic assistance which has proven beneficial in providing a safe steady-hand manipulation. Efficient assistance from the robots heavily relies on accurate sensing of surgery states (e.g. instrument tip localization and tool-to-tissue interaction forces). Many of the existing tool tip localization methods require preoperative frame registrations or instrument calibrations. In this study using an iterative approach and by combining vision and force-based methods, we develop calibration- and registration-independent (RI) algorithms to provide online estimates of instrument stiffness (least squares and adaptive). The estimations are then combined with a state-space model based on the forward kinematics (FWK) of the Steady-Hand Eye Robot (SHER) and Fiber Brag Grating (FBG) sensor measurements. This is accomplished using a Kalman Filtering (KF) approach to improve the deflected instrument tip position estimations during robot-assisted eye surgery. The conducted experiments demonstrate that when the online RI stiffness estimations are used, the instrument tip localization results surpass those obtained from pre-operative offline calibrations for stiffness.

Concepts and Trends n Autonomy for Robot-Assisted Surgery.

Surgical robots have been widely adopted with over 4000 robots being used in practice daily. However, these are telerobots that are fully controlled by skilled human surgeons. Introducing "surgeon-assist"-some forms of autonomy-has the potential to reduce tedium and increase consistency, analogous to driver-assist functions for lanekeeping, cruise control, and parking. This article examines the scientific and technical backgrounds of robotic autonomy in surgery and some ethical, social, and legal implications. We describe several autonomous surgical tasks that have been automated in laboratory settings, and research concepts and trends.

Bridging 3D Slicer and ROS2 for Image-Guided Robotic Interventions.

Developing image-guided robotic systems requires access to flexible, open-source software. For image guidance, the open-source medical imaging platform 3D Slicer is one of the most adopted tools that can be used for research and prototyping. Similarly, for robotics, the open-source middleware suite robot operating system (ROS) is the standard development framework. In the past, there have been several "ad hoc" attempts made to bridge both tools; however, they are all reliant on middleware and custom interfaces. Additionally, none of these attempts have been successful in bridging access to the full suite of tools provided by ROS or 3D Slicer. Therefore, in this paper, we present the SlicerROS2 module, which was designed for the direct use of ROS2 packages and libraries within 3D Slicer. The module was developed to enable real-time visualization of robots, accommodate different robot configurations, and facilitate data transfer in both directions (between ROS and Slicer). We demonstrate the system on multiple robots with different configurations, evaluate the system performance and discuss an image-guided robotic intervention that can be prototyped with this module. This module can serve as a starting point for clinical system development that reduces the need for custom interfaces and time-intensive platform setup.

A Dexterous Robotic System for Autonomous Debridement of Osteolytic Bone Lesions in Confined Spaces: Human Cadaver Studies.

This article presents a dexterous robotic system for autonomous debridement of osteolytic bone lesions in confined spaces. The proposed system is distinguished from the state-of-the-art orthopedics systems because it combines a rigid-link robot with a continuum manipulator (CM) that enhances reach in difficult-to-access spaces often encountered in surgery. The CM is equipped with flexible debriding instruments and fiber Bragg grating sensors. The surgeon plans on the patient's preoperative computed tomography and the robotic system performs the task autonomously under the surgeon's supervision. An optimization-based controller generates control commands on the fly to execute the task while satisfying physical and safety constraints. The system design and controller are discussed and extensive simulation, phantom and human cadaver experiments are carried out to evaluate the performance, workspace, and dexterity in confined spaces. Mean and standard deviation of target placement are 0.5 and 0.18 mm, and the robotic system covers 91% of the workspace behind an acetabular implant in treatment of hip osteolysis, compared to the 54% that is achieved by conventional rigid tools.

Characterization of patient head motion in otologic surgery: Implications for TEES.

PURPOSE: Middle ear disease is increasingly being managed via transcanal endoscopic ear surgery (TEES). A limitation of TEES is that it restricts the surgeon to single-handed dissection. One solution to this would be an endoscope holder to facilitate two-handed dissection. Current endoscope holders are stationary, and can cause potential damage from endoscope contact with the ossicles or ear canal if unintended head motion occurs from inadequate anesthetic. A dynamic device that could detect and react to patient motion would mitigate these concerns, but currently there is little formal characterization of the frequency, velocity and acceleration of unintended patient head motion during otologic procedures performed under general anesthesia. The present study aims to characterize intraoperative patient head motion kinematics during cases utilizing TEES. MATERIALS AND METHODS: This is a prospective study of adults undergoing otologic procedures performed with general anesthesia and without paralysis. Head motion was characterized using a nine-axis inertial measurement unit (IMU), (LPMS-B2, Life Performance Research) mounted to each patient's forehead for the procedure duration. RESULTS: Data was collected across 10 cases; 50% of patients were female and mean age was 50 ± 14 years. There was observed patient head motion in 40% of cases with maximum linear acceleration of 0.75 m/s2 and angular velocity of 12.50 degrees/s. CONCLUSIONS: Patient movement during otologic procedures was commonly observed, demonstrating the need for a dynamic holder to allow two-handed TEES. Results from this study are the first objective characterization of patient head motion kinematics during otologic procedures performed under general anesthesia.

Characterization of patient head motion in otologic surgery: Implications for TEES.

PURPOSE: Middle ear disease is increasingly being managed via transcanal endoscopic ear surgery (TEES). A limitation of TEES is that it restricts the surgeon to single-handed dissection. One solution to this would be an endoscope holder to facilitate two-handed dissection. Current endoscope holders are stationary, and can cause potential damage from endoscope contact with the ossicles or ear canal if unintended head motion occurs from inadequate anesthetic. A dynamic device that could detect and react to patient motion would mitigate these concerns, but currently there is little formal characterization of the frequency, velocity and acceleration of unintended patient head motion during otologic procedures performed under general anesthesia. The present study aims to characterize intraoperative patient head motion kinematics during cases utilizing TEES. MATERIALS AND METHODS: This is a prospective study of adults undergoing otologic procedures performed with general anesthesia and without paralysis. Head motion was characterized using a nine-axis inertial measurement unit (IMU), (LPMS-B2, Life Performance Research) mounted to each patient's forehead for the procedure duration. RESULTS: Data was collected across 10 cases; 50% of patients were female and mean age was 50 ± 14 years. There was observed patient head motion in 40% of cases with maximum linear acceleration of 0.75 m/s2 and angular velocity of 12.50 degrees/s. CONCLUSIONS: Patient movement during otologic procedures was commonly observed, demonstrating the need for a dynamic holder to allow two-handed TEES. Results from this study are the first objective characterization of patient head motion kinematics during otologic procedures performed under general anesthesia.

Data-Driven Shape Sensing of a Surgical Continuum Manipulator Using an Uncalibrated Fiber Bragg Grating Sensor.

This article proposes a data-driven learning-based approach for shape sensing and Distal-end Position Estimation (DPE) of a surgical Continuum Manipulator (CM) in constrained environments using Fiber Bragg Grating (FBG) sensors. The proposed approach uses only the sensory data from an unmodeled uncalibrated sensor embedded in the CM to estimate the shape and DPE. It serves as an alternate to the conventional mechanics-based sensor-model-dependent approach which relies on several sensor and CM geometrical assumptions. Unlike the conventional approach where the shape is reconstructed from proximal to distal end of the device, we propose a reversed approach where the distal-end position is estimated first and given this information, shape is then reconstructed from distal to proximal end. The proposed methodology yields more accurate DPE by avoiding accumulation of integration errors in conventional approaches. We study three data-driven models, namely a linear regression model, a Deep Neural Network (DNN), and a Temporal Neural Network (TNN) and compare DPE and shape reconstruction results. Additionally, we test both approaches (data-driven and model-dependent) against internal and external disturbances to the CM and its environment such as incorporation of flexible medical instruments into the CM and contacts with obstacles in taskspace. Using the data-driven (DNN) and model-dependent approaches, the following max absolute errors are observed for DPE: 0.78 mm and 2.45 mm in free bending motion, 0.11 mm and 3.20 mm with flexible instruments, and 1.22 mm and 3.19 mm with taskspace obstacles, indicating superior performance of the proposed data-driven approach compared to the conventional approaches.

A Surgical Robotic System for Treatment of Pelvic Osteolysis Using an FBG-Equipped Continuum Manipulator and Flexible Instruments.

This paper presents the development and experimental evaluation of a redundant robotic system for the less-invasive treatment of osteolysis (bone degradation) behind the acetabular implant during total hip replacement revision surgery. The system comprises a rigid-link positioning robot and a Continuum Dexterous Manipulator (CDM) equipped with highly flexible debriding tools and a Fiber Bragg Grating (FBG)-based sensor. The robot and the continuum manipulator are controlled concurrently via an optimization-based framework using the Tip Position Estimation (TPE) from the FBG sensor as feedback. Performance of the system is evaluated on a setup that consists of an acetabular cup and saw-bone phantom simulating the bone behind the cup. Experiments consist of performing the surgical procedure on the simulated phantom setup. CDM TPE using FBGs, target location placement, cutting performance, and the concurrent control algorithm capability in achieving the desired tasks are evaluated. Mean and standard deviation of the CDM TPE from the FBG sensor and the robotic system are 0.50 mm, and 0.18 mm, respectively. Using the developed surgical system, accurate positioning and successful cutting of desired straight-line and curvilinear paths on saw-bone phantoms behind the cup with different densities are demonstrated. Compared to the conventional rigid tools, the workspace reach behind the acetabular cup is 2.47 times greater when using the developed robotic system.

A Mosquito Pick-and-Place System for PfSPZ-based Malaria Vaccine Production.

The treatment of malaria is a global health challenge that stands to benefit from the widespread introduction of a vaccine for the disease. A method has been developed to create a live organism vaccine using the sporozoites (SPZ) of the parasite Plasmodium falciparum (Pf), which are concentrated in the salivary glands of infected mosquitoes. Current manual dissection methods to obtain these PfSPZ are not optimally efficient for large-scale vaccine production. We propose an improved dissection procedure and a mechanical fixture that increases the rate of mosquito dissection and helps to deskill this stage of the production process. We further demonstrate the automation of a key step in this production process, the picking and placing of mosquitoes from a staging apparatus into a dissection assembly. This unit test of a robotic mosquito pick-and-place system is performed using a custom-designed micro-gripper attached to a four degree of freedom (4-DOF) robot under the guidance of a computer vision system. Mosquitoes are autonomously grasped and pulled to a pair of notched dissection blades to remove the head of the mosquito, allowing access to the salivary glands. Placement into these blades is adapted based on output from computer vision to accommodate for the unique anatomy and orientation of each grasped mosquito. In this pilot test of the system on 50 mosquitoes, we demonstrate a 100% grasping accuracy and a 90% accuracy in placing the mosquito with its neck within the blade notches such that the head can be removed. This is a promising result for this difficult and non-standard pick-and-place task. NOTE TO PRACTITIONERS­: Automated processes could help increase malaria vaccine production to global scale. Currently, production requires technicians to manually dissect mosquitoes, a process that is slow, tedious, and requires a lengthy training regimen. This paper presents an an improved manual fixture and procedure that reduces technician training time. Further, an approach to automate this dissection process is proposed and the critical step of robotic manipulation of the mosquito with the aid of computer vision is demonstrated. Our approach may serve as a useful example of system design and integration for practitioners that seek to perform new and challenging pick-and-place tasks with small, non-uniform, and highly deformable objects.

Clinical outcomes and serologic response in solid organ transplant recipients with COVID-19: A case series from the United States.

The coronavirus disease 2019 (COVID-19) pandemic caused by SARS coronavirus 2 (SARS-CoV-2) has caused significant morbidity and mortality for patients and stressed healthcare systems worldwide. The clinical features, disease course, and serologic response of COVID-19 among immunosuppressed patients such as solid organ transplant (SOT) recipients, who are at presumed risk for more severe disease, are not well characterized. We describe our institutional experience with COVID-19 among 10 SOT patients, including the clinical presentation, treatment modalities, and outcomes of 7 renal transplant recipients, 1 liver transplant recipient, 1 heart transplant recipient, and 1 lung transplant recipient. In addition, we report the serologic response in SOT recipients, documenting a positive IgG response in all 7 hospitalized patients. We also review the existing literature on COVID-19 in SOT recipients to consolidate the current knowledge on COVID-19 in the SOT population for the transplant community.

Framework Effects on Activation and Functionalisation of Methane in Zinc-Exchanged Zeolites.

The first selective oxidation of methane to methanol is reported herein for zinc-exchanged MOR (Zn/MOR). Under identical conditions, Zn/FER and Zn/ZSM-5 both form zinc formate and methanol. Selective methane activation to form [Zn-CH3 ]+ species was confirmed by 13 C MAS NMR spectroscopy for all three frameworks. The percentage of active zinc sites, measured through quantitative NMR spectroscopy studies, varied with the zeolite framework and was found to be ZSM-5 (5.7 %), MOR (1.2 %) and FER (0.5 %). For Zn/MOR, two signals were observed in the 13 C MAS NMR spectrum, resulting from two distinct [Zn-CH3 ]+ species present in the 12 MR and 8 MR side pockets, as supported by additional NMR experiments. The observed products of oxidation of the [Zn-CH3 ]+ species are shown to depend on the zeolite framework type and the oxidative conditions used. These results lay the foundation for developing structure-function correlations for methane conversion over zinc-exchanged zeolites.

Mapping and assessing the impact of small-scale ephemeral water sources on wildlife in an African seasonal savannah.

In many savannah regions of Africa, pronounced seasonal variability in rainfall results in wildlife being restricted to floodplains and other habitats adjacent to permanent surface water in the dry season. During the wet season, rainfall fills small-scale, ephemeral water sources that allow wildlife to exploit forage and other resources far from permanent surface water. These water sources remain difficult to quantify, however, due to their small and ephemeral nature, and as a result are rarely included in quantitative studies of wildlife distribution, abundance, and movement. Our goal was to map ephemeral water in Bwabwata National Park in Namibia using two different approaches and to relate measures of ephemeral water to the abundance, distribution, and movement of two large wildlife species. We used high-resolution Google Earth and Esri World imagery to visually identify waterholes. Additionally, we used Sentinel-2 satellite imagery to map ephemeral water across the study area using the Normalized Difference Water Index. With these mapped waterhole layers and data from GPS-collared individuals of African elephant (Loxodonta africana) and African buffalo (Syncerus caffer), we evaluated the importance of ephemeral water in conditioning abundance and movement of these two species. The two approaches to mapping ephemeral water resulted in the visual identification of nearly 10,000 waterholes, and a predicted ephemeral water layer of ~76% accuracy. The inclusion of ephemeral water into models of abundance and movement resulted in improved goodness of fit relative to those without water, and water impacts on abundance and movement were among the strongest of all variables considered. The potential importance of ephemeral water in conditioning the movements and distributions of large herbivores in African savannahs has been difficult to quantify relative to vegetation drivers. Our results suggest research into ephemeral water impacts deserves more attention.

SCADE: Simultaneous Sensor Calibration and Deformation Estimation of FBG-Equipped Unmodeled Continuum Manipulators.

In this article, we present a novel stochastic algorithm called simultaneous sensor calibration and deformation estimation (SCADE) to address the problem of modeling deformation behavior of a generic continuum manipulator (CM) in free and obstructed environments. In SCADE, using a novel mathematical formulation, we introduce a priori model-independent filtering algorithm to fuse the continuous and inaccurate measurements of an embedded sensor (e.g., magnetic or piezoelectric sensors) with an intermittent but accurate data of an external imaging system (e.g., optical trackers or cameras). The main motivation of this article is the crucial need of obtaining an accurate shape/position estimation of a CM utilized in a surgical intervention. In these robotic procedures, the CM is typically equipped with an embedded sensing unit (ESU) while an external imaging modality (e.g., ultrasound or a fluoroscopy machine) is also available in the surgical site. The results of two different set of prior experiments in free and obstructed environments were used to evaluate the efficacy of SCADE algorithm. The experiments were performed with a CM specifically designed for orthopaedic interventions equipped with an inaccurate Fiber Bragg Grating (FBG) ESU and overhead camera. The results demonstrated the successful performance of the SCADE algorithm in simultaneous estimation of unknown deformation behavior of the utilized unmodeled CM together with realizing the time-varying drift of the poor-calibrated FBG sensing unit. Moreover, the results showed the phenomenal out-performance of the SCADE algorithm in estimation of the CM's tip position as compared to FBG-based position estimations.

Biomechanical Guidance System for Periacetabular Osteotomy.

This chapter presents a biomechanical guidance navigation system for performing periacetabular osteotomy (PAO) to treat developmental dysplasia of the hip. The main motivation of the biomechanical guidance system (BGS) is to plan and track the osteotomized fragment in real time during PAO while simplifying this challenging procedure. The BGS computes the three-dimensional position of the osteotomized fragment in terms of conventional anatomical angles and simulates biomechanical states of the joint. This chapter describes the BGS structure and its application using two different navigation approaches including optical tracking of the fragment and x-ray-based navigation. Both cadaver studies and preliminary clinical studies showed that the biomechanical planning is consistent with traditional PAO planning techniques and that the additional information provided by accurate 3D positioning of the fragment does not adversely impact the surgery.

3-DOF Force-Sensing Motorized Micro-Forceps for Robot-Assisted Vitreoretinal Surgery.

In vitreoretinal surgery, membrane peeling is a prototypical task where a layer of fibrous tissue is delaminated off the retina with a micro-forceps by applying very fine forces that are mostly imperceptible to the surgeon. Previously we developed sensitized ophthalmic surgery tools based on fiber Bragg grating (FBG) strain sensors, which were shown to precisely detect forces at the instrument's tip in two degrees of freedom perpendicular to the tool axis. This paper presents a new design that employs an additional sensor to capture also the tensile force along the tool axis. The grasping functionality is provided via a compact motorized unit. To compute forces, we investigate two distinct fitting methods: a linear regression and a nonlinear fitting based on second-order Bernstein polynomials. We carry out experiments to test the repeatability of sensor outputs, calibrate the sensor and validate its performance. Results demonstrate sensor wavelength repeatability within 2 pm. Although the linear method provides sufficient accuracy in measuring transverse forces, in the axial direction it produces a root mean square (rms) error over 3 mN even for a confined magnitude and direction of forces. On the other hand, the nonlinear method provides a more consistent and accurate measurement of both the transverse and axial forces for the entire force range (0-25 mN). Validation including random samples shows that our tool with the nonlinear force computation method can predict 3-D forces with an rms error under 0.15 mN in the transverse plane and within 2 mN accuracy in the axial direction.

Towards Robot-Assisted Retinal Vein Cannulation: A Motorized Force-Sensing Microneedle Integrated with a Handheld Micromanipulator †.

Retinal vein cannulation is a technically demanding surgical procedure where therapeutic agents are injected into the retinal veins to treat occlusions. The clinical feasibility of this approach has been largely limited by the technical challenges associated with performing the procedure. Among the challenges to successful vein cannulation are identifying the moment of venous puncture, achieving cannulation of the micro-vessel, and maintaining cannulation throughout drug delivery. Recent advances in medical robotics and sensing of tool-tissue interaction forces have the potential to address each of these challenges as well as to prevent tissue trauma, minimize complications, diminish surgeon effort, and ultimately promote successful retinal vein cannulation. In this paper, we develop an assistive system combining a handheld micromanipulator, called "Micron", with a force-sensing microneedle. Using this system, we examine two distinct methods of precisely detecting the instant of venous puncture. This is based on measured tool-tissue interaction forces and also the tracked position of the needle tip. In addition to the existing tremor canceling function of Micron, a new control method is implemented to actively compensate unintended movements of the operator, and to keep the cannulation device securely inside the vein following cannulation. To demonstrate the capabilities and performance of our uniquely upgraded system, we present a multi-user artificial phantom study with subjects from three different surgical skill levels. Results show that our puncture detection algorithm, when combined with the active positive holding feature enables sustained cannulation which is most evident in smaller veins. Notable is that the active holding function significantly attenuates tool motion in the vein, thereby reduces the trauma during cannulation.

Motorized Micro-Forceps with Active Motion Guidance based on Common-Path SSOCT for Epiretinal Membranectomy.

In this study, we built and tested a handheld motion-guided micro-forceps system using common-path swept source optical coherence tomography (CP-SSOCT) for highly accurate depth controlled epiretinal membranectomy. A touch sensor and two motors were used in the forceps design to minimize the inherent motion artifact while squeezing the tool handle to actuate the tool and grasp, and to independently control the depth of the tool-tip. A smart motion monitoring and a guiding algorithm were devised to provide precise and intuitive freehand control. We compared the involuntary tool-tip motion occurring while grasping with a standard manual micro-forceps and our touch sensor activated micro-forceps. The results showed that our touch-sensor-based and motor-actuated tool can significantly attenuate the motion artifact during grasping (119.81 µm with our device versus 330.73 µm with the standard micro-forceps). By activating the CP-SSOCT based depth locking feature, the erroneous tool-tip motion can be further reduced down to 5.11µm. We evaluated the performance of our device in comparison to the standard instrument in terms of the elapsed time, the number of grasping attempts, and the maximum depth of damage created on the substrate surface while trying to pick up small pieces of fibers (Ø 125 µm) from a soft polymer surface. The results indicate that all metrics were significantly improved when using our device; of note, the average elapsed time, the number of grasping attempts, and the maximum depth of damage were reduced by 25%, 31%, and 75%, respectively.

Ezh2 maintains retinal progenitor proliferation, transcriptional integrity, and the timing of late differentiation.

Epigenetic regulation, including histone modification, is a critical component of gene regulation, although precisely how this contributes to the development of complex tissues such as the neural retina is still being explored. We show that during retinal development in mouse, there are dynamic patterns of expression of the polycomb repressive complex 2 (PRC2) catalytic subunit EZH2 in retinal progenitors and some differentiated cells, as well as dynamic changes in the histone modification H3K27me3. Using conditional knockout of Ezh2 using either Pax6-αCre or Six3-Cre, we find selective reduction in postnatal retinal progenitor proliferation, disruption of retinal lamination, and enhanced differentiation of several late born cell types in the early postnatal retina, including photoreceptors and Müller glia, which are ultimately increased in number and become reactive. RNA-seq identifies many non-retinal genes upregulated with loss of Ezh2, including multiple Hox genes and the cell cycle regulator Cdkn2a, which are established targets of EZH2-mediated repression. ChIP analysis confirms loss of the H3K27me3 modification at these loci. Similar gene upregulation is observed in retinal explants treated with an EZH2 chemical inhibitor. There is considerable overlap with EZH2-regulated genes reported in non-neural tissues, suggesting that EZH2 can regulate similar genes in multiple lineages. Our findings reveal a conserved role for EZH2 in constraining the expression of potent developmental regulators to maintain lineage integrity and retinal progenitor proliferation, as well as regulating the timing of late differentiation.

ASCL1 reprograms mouse Muller glia into neurogenic retinal progenitors.

Non-mammalian vertebrates have a robust ability to regenerate injured retinal neurons from Müller glia (MG) that activate the gene encoding the proneural factor Achaete-scute homolog 1 (Ascl1; also known as Mash1 in mammals) and de-differentiate into progenitor cells. By contrast, mammalian MG have a limited regenerative response and fail to upregulate Ascl1 after injury. To test whether ASCL1 could restore neurogenic potential to mammalian MG, we overexpressed ASCL1 in dissociated mouse MG cultures and intact retinal explants. ASCL1-infected MG upregulated retinal progenitor-specific genes and downregulated glial genes. Furthermore, ASCL1 remodeled the chromatin at its targets from a repressive to an active configuration. MG-derived progenitors differentiated into cells that exhibited neuronal morphologies, expressed retinal subtype-specific neuronal markers and displayed neuron-like physiological responses. These results indicate that a single transcription factor, ASCL1, can induce a neurogenic state in mature MG.