About

Glen Prusky, M.Sc., Ph.D., is a Professor of Physiology and Biophysics at Weill Cornell Medicine. His research focuses on understanding the nature of adaptive change in the nervous system, primarily using the rodent visual system as a model. His lab combines cellular, electrophysiological, and theoretical methodologies with measures of behavior in freely-moving animals to investigate experience-dependent plasticity of vision. Current research includes manipulating the function of the retina and visual cortex to establish substrates underlying developmental and adult visual plasticity, as well as developing treatments for retinal degenerative diseases through cell-based retinal transplantation methods that circumvent immune barriers. Additionally, his work involves developing rehabilitative strategies for stroke, with a focus on how pre-stroke visual experience influences recovery. His research also explores mechanisms underlying visual discrimination learning, visual recognition memory, cross-modal plasticity, and retinal coding. Dr. Prusky's contributions extend to testing hypotheses related to visual function and plasticity, aiming to advance understanding and treatment of visual impairments and neuroplasticity in the nervous system.

Research topics

• Neuroscience
• Psychology
• Biology
• Medicine
• Audiology

Selected publications

• IND-enabling safety and efficacy of RPESC-RPE-4W, an adult RPE progenitor cell therapy for dry age-related macular degeneration

  Cell Reports Medicine · 2026-05-01

  articleOpen access

  Dry age-related macular degeneration (AMD) is a prevalent blinding disorder characterized by loss of retinal pigment epithelium (RPE) cells and resulting central vision impairment. Here, we describe preclinical studies supporting an investigational new drug (IND) application for adult RPE stem cell-derived RPE (RPESC-RPE) cell replacement therapy. We establish donor-to-donor reproducibility and Good Manufacturing Practice (GMP) processes and evaluate the GMP cell product in preclinical studies conducted in accordance with Good Laboratory Practice principles. Efficacy experiments in Royal College of Surgeons rats show that subretinal implantation of the 4-week, postmitotic, progenitor-stage product (RPESC-RPE-4W) produces significant and durable vision rescue compared to vehicle control. Biodistribution and safety studies in immunocompromised Rowett Nude rats demonstrate a favorable safety profile, with no adverse effects related to the cell product. These studies underpin allowance of an ongoing phase 1/2a clinical trial.

  PublisherDOI

• Quantitative patterns of visual impairment and recovery in children with brain injury

  Research Square · 2024-07-30

  preprintOpen access1st authorCorresponding
  PublisherOA PDFDOI

• Identifying biomarkers of heterogeneity and transplantation efficacy in retinal pigment epithelial cells

  The Journal of Experimental Medicine · 2023-09-20 · 22 citations

  articleOpen access

  Transplantation of retinal pigment epithelial (RPE) cells holds great promise for patients with retinal degenerative diseases, such as age-related macular degeneration. In-depth characterization of RPE cell product identity and critical quality attributes are needed to enhance efficacy and safety of replacement therapy strategies. Here, we characterized an adult RPE stem cell-derived (RPESC-RPE) cell product using bulk and single-cell RNA sequencing (scRNA-seq), assessing functional cell integration in vitro into a mature RPE monolayer and in vivo efficacy by vision rescue in the Royal College of Surgeons rats. scRNA-seq revealed several distinct subpopulations in the RPESC-RPE product, some with progenitor markers. We identified RPE clusters expressing genes associated with in vivo efficacy and increased cell integration capability. Gene expression analysis revealed lncRNA (TREX) as a predictive marker of in vivo efficacy. TREX knockdown decreased cell integration while overexpression increased integration in vitro and improved vision rescue in the RCS rats.

  PublisherOA PDFDOI

• Retinoschisin Deficiency Induces Persistent Aberrant Waves of Activity Affecting Neuroglial Signaling in the Retina

  Journal of Neuroscience · 2022-07-29 · 19 citations

  articleOpen access

  Genetic disorders that present during development make treatment strategies particularly challenging because there is a need to disentangle primary pathophysiology from downstream dysfunction caused at key developmental stages. To provide a deeper insight into this question, we studied a mouse model of X-linked juvenile retinoschisis, an early-onset inherited condition caused by mutations in the Rs1 gene encoding retinoschisin (RS1) and characterized by cystic retinal lesions and early visual deficits. Using an unbiased approach in expressing the fast intracellular calcium indicator GCaMP6f in neuronal, glial, and vascular cells of the retina of RS1-deficient male mice, we found that initial cyst formation is paralleled by the appearance of aberrant spontaneous neuroglial signals as early as postnatal day 15, when eyes normally open. These presented as glutamate-driven wavelets of neuronal activity and sporadic radial bursts of activity by Mller glia, spanning all retinal layers and disrupting light-induced signaling. This study confers a role to RS1 beyond its function as an adhesion molecule, identifies an early onset for dysfunction in the course of disease, establishing a potential window for disease diagnosis and therapeutic intervention.

  PublisherOA PDFDOI

• Identifying Biomarkers of Retinal Pigment Epithelial Cell Stem Cell-derived RPE Cell Heterogeneity and Transplantation Efficacy

  bioRxiv (Cold Spring Harbor Laboratory) · 2022-11-23 · 2 citations

  preprintOpen access

  Summary Transplantation of retinal pigment epithelial (RPE) cells holds great promise for patients with retinal degenerative diseases such as age-related macular degeneration. In-depth characterization of RPE cell product identity and critical quality attributes are needed to enhance efficacy and safety of replacement therapy strategies. Here we characterized an adult RPE stem cell-derived (RPESC-RPE) cell product using bulk and single cell RNA sequencing (sc-RNA-seq), assessing functional cell integration in vitro into a mature RPE monolayer and in vivo efficacy by vision rescue in the Royal College of Surgeons rats. scRNA-seq revealed several distinct subpopulations in the RPESC-RPE product, some with progenitor markers. We identified RPE clusters expressing genes associated with in vivo efficacy and increased cell integration capability. Gene expression analysis revealed a lncRNA (TREX) as a predictive marker of in vivo efficacy. TREX knockdown decreased cell integration while overexpression increased integration in vitro and improved vision rescue in the RCS rats.

  PublisherOA PDFDOI

• Contrast sensitivity assessment in children with brain injury.

  2021-06-21

  articleSenior author

• : A neuroscientist's sound toolkit

  Heliyon · 2021-02-01 · 9 citations

  articleOpen accessSenior author

  In neuroscientific experiments and applications, working with auditory stimuli demands software tools for generation and acquisition of raw audio, for composition and tailoring of that material into finished stimuli, for precisely timed presentation of the stimuli, and for experimental session recording. Numerous programming tools exist to approach these tasks, but their differing specializations and conventions demand extra time and effort for integration. In particular, verifying stimulus timing requires extensive engineering effort when developing new applications.This paper has two purposes. The first is to present audiomath (https://pypi.org/project/audiomath), a sound software library for Python that prioritizes the needs of neuroscientists. It minimizes programming effort by providing a simple object-oriented interface that unifies functionality for audio generation, manipulation, visualization, decoding, encoding, recording, and playback. It also incorporates specialized tools for measuring and optimizing stimulus timing.The second purpose is to relay what we have learned, during development and application of the software, about the twin challenges of delivering stimuli precisely at a certain time, and of precisely measuring the time at which stimuli were delivered. We provide a primer on these problems and the possible approaches to them. We then report audio latency measurements across a range of hardware, operating systems and settings, to illustrate the ways in which hardware and software factors interact to affect stimulus presentation performance, and the resulting pitfalls for the programmer and experimenter. In particular, we highlight the potential conflict between demands for low latency, low variability in latency (“jitter”), cooperativeness, and robustness. We report the ways in which audiomath can help to map this territory and provide a simplified path toward each application's particular priority.By unifying audio-related functionality and providing specialized diagnostic tools, audiomath both simplifies and potentiates the development of neuroscientific applications in Python.

  PublisherOA PDFDOI

• Treatment of age-related visual impairment with a peptide acting on mitochondria

  Disease Models & Mechanisms · 2021-11-12 · 17 citations

  articleOpen accessSenior author

  Age-related visual decline and disease due to neural dysfunction are major sources of disability that have resisted effective treatment. In light of evidence that visual impairment and mitochondrial dysfunction advance with age, we characterized age-related decline of spatial visual function in mice and investigated whether treatment of aged mice with the mitochondrion-penetrating peptide elamipretide that has been reported to improve mitochondrial function, would improve it. Impaired photopic acuity measured by using a virtual optokinetic system emerged near 18 months and declined to ∼40% below normal by 34 months. Daily application of the synthetic peptide elamipretide, which has high selectivity for mitochondrial membranes that contain cardiolipin and promotes efficient electron transfer, was able to mitigate visual decline from 18 months onwards. Daily application from 24 months onwards, i.e. when acuity had reduced by ∼16%, reversed visual decline and normalized function within 2 months. Recovered function persisted for at least 3 months after treatment was withdrawn and a single treatment at 24 months delayed subsequent visual decline. Elamipretide applied daily from 32 months onwards took longer to take effect, but substantial improvement was found within 2 months. The effects of age and elamipretide treatment on contrast sensitivity were similar to those on acuity, systemic and eye drop applications of elamipretide had comparable effects, scotopic spatial visual function was largely unaffected by age or treatment, and altered function was independent of variation in optical clarity. These data indicate that elamipretide treatment adaptively alters the aging visual system. They also provide a rationale to investigate whether mitochondrial dysfunction is a treatable pathophysiology of human visual aging and age-related visual disease.

  PublisherOA PDFDOI

• Tracking-Based Interactive Assessment of Saccades, Pursuits, Visual Field, and Contrast Sensitivity in Children With Brain Injury

  Frontiers in Human Neuroscience · 2021-10-29 · 22 citations

  articleOpen accessSenior authorCorresponding

  Visual deficits in children that result from brain injury, including cerebral/cortical visual impairment (CVI), are difficult to assess through conventional methods due to their frequent co-occurrence with cognitive and communicative disabilities. Such impairments hence often go undiagnosed or are only determined through subjective evaluations of gaze-based reactions to different forms, colors, and movements, which limits any potential for remediation. Here, we describe a novel approach to grading visual health based on eye movements and evidence from gaze-based tracking behaviors. Our approach-the "Visual Ladder"-reduces reliance on the user's ability to attend and communicate. The Visual Ladder produces metrics that quantify spontaneous saccades and pursuits, assess visual field responsiveness, and grade spatial visual function from tracking responses to moving stimuli. We used the Ladder to assess fourteen hospitalized children aged 3 to 18 years with a diverse range of visual impairments and causes of brain injury. Four children were excluded from analysis due to incompatibility with the eye tracker (e.g., due to severe strabismus). The remaining ten children-including five non-verbal children-were tested multiple times over periods ranging from 2 weeks to 9 months, and all produced interpretable outcomes on at least three of the five visual tasks. The results suggest that our assessment tasks are viable in non-communicative children, provided their eyes can be tracked, and hence are promising tools for use in a larger clinical study. We highlight and discuss informative outcomes exhibited by each child, including directional biases in eye movements, pathological nystagmus, visual field asymmetries, and contrast sensitivity deficits. Our findings indicate that these methodologies will enable the rapid, objective classification and grading of visual impairments in children with CVI, including non-verbal children who are currently precluded from most vision assessments. This would provide a much-needed differential diagnostic and prognostic tool for CVI and other impairments of the visual system, both ocular and cerebral.

  PublisherDOI

• Gradiate: A radial sweep approach to measuring detailed contrast sensitivity functions from eye movements

  Journal of Vision · 2020-12-28 · 15 citations

  articleOpen accessSenior author

  The contrast sensitivity function (CSF) is an informative measure of visual health, but the practical difficulty of measuring it has impeded detailed analyses of its relationship to different visual disorders. Furthermore, most existing tasks cannot be used in populations with cognitive impairment. We analyzed detailed CSFs measured with a nonverbal procedure called "Gradiate," which efficiently infers visibility from eye movements and manipulates stimulus appearance in real time. Sixty observers of varying age (38 with refractive error) were presented with moving stimuli. Stimulus spatial frequency and contrast advanced along 15 radial sweeps through CSF space in response to stimulus-congruent eye movements. A point on the CSF was recorded when tracking ceased. Gradiate CSFs were reliable and in high agreement with independent low-contrast acuity thresholds. Overall CSF variation was largely captured by two orthogonal factors ("radius" and "slope") or two orthogonal shape factors when size was normalized ("aspect ratio" and "curvature"). CSF radius was highly predictive of LogMAR acuity, as were aspect ratio and curvature together, but only radius was predictive of observer age. Our findings suggest that Gradiate holds promise for assessing spatial vision in both verbal and nonverbal populations and indicate that variation between detailed CSFs can reveal useful information about visual health.

  PublisherDOI

Recent grants

• Grading visual impairment in children with brain injury

  NIH · $3.1M · 2019–2024

• Automated Assessment of Visuomotor Function in Children with Brain Injury

  NIH · $581k · 2016–2018

Frequent coauthors

• Nazia M. Alam

  Burke Medical Research Institute

  104 shared

• Scott W.J. Mooney

  Burke Medical Research Institute

  76 shared

• Matthew M. LaVail

  University of California, San Francisco

  70 shared

• Anna‐Sophia Kiang

  Trinity College Dublin

  64 shared

• Krisztina Valter

  Australian National University

  64 shared

• Wei Cao

  Changzhou No.2 People's Hospital

  64 shared

• Qin Ding

  Third Xiangya Hospital

  64 shared

• Peter Humphries

  64 shared