
Wendy Liu, MD, PhD
Assistant Professor of Ophthalmology
Web page: http://web.stanford.edu/people/wwhliu
Bio
Dr. Wendy Liu, MD, PhD, is a clinician-scientist and fellowship-trained glaucoma and cataract surgeon. Dr. Liu engages in translational research with the goal of finding new druggable targets in glaucoma treatment. Her interests include the role of mechanosensation in the eye as it relates to the pathophysiology of glaucoma, and discovery of novel wound modulating agents for glaucoma surgery. She is a Stanford KL2 Scholar.
Her clinical practice focuses on management of adult glaucoma and cataracts. She specializes in traditional glaucoma surgery as well as minimally-invasive glaucoma surgery, such as iStent, Hydrus, Xen, KDB, OMNI, and GATT. Her goal is to work together with patients to determine what the best treatment options are for them, so they can maintain the best vision and quality of life.
Dr. Liu graduated summa cum laude from Princeton University with a degree in Molecular Biology and certificates in biophysics, materials science and engineering. She received several awards for excellence in academics and research, including the Shapiro Award for Academic Excellence, the American Society for Microbiology Undergraduate Research Fellowship, and the Sigma Xi Book Award for the best senior thesis. She subsequently earned her MD with honors from Harvard Medical School in the Harvard-MIT Program in Health Sciences and Technology, and PhD in Neurobiology from Harvard University. At Harvard, she was awarded the Presidential Scholarship and Martha Gray Prize for Excellence in Research. She was selected to receive a Howard Hughes Medical Institute research fellowship for her PhD work, which led to the discovery of novel thermosensory and olfactory circuits in the fruit fly using in vivo electrophysiology. She completed her ophthalmology residency at Massachusetts Eye and Ear, where she was awarded the Gragoudas Folkman Award for the best research grant proposal. She completed her glaucoma fellowship at Wills Eye Hospital.
Dr. Liu has published first-author articles in journals including New England Journal of Medicine, Nature, Proceedings of the National Academy of Sciences, and Current Biology. She is a member of the American Academy of Ophthalmology, the Association for Research in Vision and Ophthalmology, and the American Glaucoma Society.
Clinical Focus
- Ophthalmology
- Glaucoma
- Cataracts
- Minimally Invasive Surgical Procedures
Academic Appointments
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Assistant Professor - University Medical Line, Ophthalmology
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Member, Bio-X
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Member, SPARK at Stanford
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Member, Wu Tsai Neurosciences Institute
Honors & Awards
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Shaffer Grant Award, Glaucoma Research Foundation
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E. Matilda Ziegler Foundation Award, E. Matilda Ziegler Foundation for the Blind
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Career Development Award, Research to Prevent Blindness
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Young Clinician Scientist Grant, American Glaucoma Society
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Spark Translational Research Grant, Stanford University
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KL2 Career Development Award, Stanford University
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Mentoring for the Advancement of Physician Scientists Grant, American Glaucoma Society
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Heed Ophthalmic Foundation Residents Retreat, Heed Ophthalmic Foundation
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Gragoudas-Folkman Award, Massachusetts Eye and Ear
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Martha Gray Prize for Excellence in Research, Harvard Medical School
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Presidential Scholarship, Harvard Medical School
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International Student Research Fellowship, Howard Hughes Medical Institute
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Graduated Summa Cum Laude with Highest Honors in Molecular Biology, Princeton University
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Certificates in Biophysics, Materials Science and Engineering, Princeton University
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George Khoury ’65 Prize for Academic Excellence, Princeton University
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Sigma Xi Book Award for best senior thesis in Molecular Biology, Princeton University
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Phi Beta Kappa, Princeton University
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Sigma Xi, Princeton University
Professional Education
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Board Certification, American Board of Ophthalmology, Ophthalmology
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Fellowship, Wills Eye Hospital, Glaucoma
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Residency, Massachusetts Eye and Ear, Ophthalmology
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Internship, Beth Israel Deaconess Medical Center, Internal Medicine
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MD, Harvard Medical School, Medicine
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PhD, Harvard University, Neurobiology
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AB, Princeton University, Molecular Biology
Current Research and Scholarly Interests
Dr. Liu's research interests include the role of mechanosensation in the eye as it relates to the pathophysiology of glaucoma, with the goal of finding new druggable targets in glaucoma treatment.
Questions we are interested in studying include:
1) What are the ion channels that mediate pressure sensing in the eye?
2) What physiological roles do these channels play in the eye?
3) How do these ion channels mediate the development of ocular pathologies?
We study these questions using a combination of techniques including patch clamp electrophysiology, molecular biology, human genetics, and animal models of glaucoma and other ocular diseases.
** We are currently looking for postdoctoral fellows and researchers to join our group. Highly motivated candidates with expertise in techniques such as eye and brain histology, molecular and cellular biology, patch clamp electrophysiology, calcium imaging and animal handling experience are encouraged to apply.
Requirements: Completion of PhD, MD, or MD PhD training. Previous experience in vision or neuroscience research is ideal.
How to Apply: Please send a copy of your CV (please include list of publications, research skills, and contact for 3 references) to: Dr. Wendy Liu wendywliu@stanford.edu **
Stanford Advisees
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Postdoctoral Faculty Sponsor
Julian Garcia, Saeed Nourmohammadi -
Doctoral Dissertation Reader (NonAC)
Emma Theisen
All Publications
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Correlation between central visual field defects and stereopsis in patients with early to moderate visual field loss.
Ophthalmology. Glaucoma
2023
Abstract
To investigate an association between stereoacuity and the presence of central visual field defects (CVFDs) due to glaucoma.Prospective, cross-sectional cohort study.Participants with early to moderate glaucoma with visual acuity better than 20/40, less than 2-line difference in visual acuity between eyes, and 2 reliable Humphrey VFs (24-2 SITA standard) with mean deviation (MD) in the worse eye better than -12dB.Stereoacuity was measured using the Titmus stereo test. Participants with a significant field defect (P<0.5%) in any one of the central four points in the 24-2 SITA standard total deviation map in either eye were classified as having a CVFD. Vision-related quality of life (VR-QOL) was measured by the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) scores. Logistic regression was used to determine the association between level of stereoacuity and age, gender, race, glaucoma type, presence of CVFDs, visual acuity, contrast sensitivity, and visual field MD.Stereoacuity in the CVFD and no CVFD groups.Sixty-five participants met the inclusion criteria. The mean age was 64.3 ± 8.0 years and 64.6% were women. Median stereoacuity was 60 arc sec (inter-quartile range 40-120). Forty-two (65%) patients had CVFDs and 23 (35%) patients did not. Median stereoacuity for the CVFD group was worse than the non-CVFD group (60 arc sec (IQR 50-140) vs. 40 arc sec (IQR 40-80); p=0.001), respectively. The non-CVFD group had a higher percentage of participants with normal stereopsis compared to the non-CVFD group (61% vs 21%, p=0.001). Multivariable analysis found that the presence of CVFDs was associated with worse stereopsis level (odds ratio 4.49, p=0.021). The CVFD group had a lower VFQ-25 composite score (84.0 vs 91.4, p=0.004), and lower VFQ-25 sub-scale scores for general vision, near activities, and mental health (P<0.05).CVFDs were associated with increased odds of poor stereoacuity in patients with early to moderate glaucomatous VF loss. Specifically, patients without CVFDs are more likely to have normal stereopsis and higher VR-QOL than those with CVFDs. Patients with CVFDs should be counseled regarding how depth perception difficulties may affect daily living.
View details for DOI 10.1016/j.ogla.2023.04.003
View details for PubMedID 37080537
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4-year Surgical Outcomes of Gonioscopy-assisted Transluminal Trabeculotomy (GATT) in Patients with Open-angle Glaucoma.
Ophthalmology. Glaucoma
2023
Abstract
To provide 4-year data on the efficacy and safety of gonioscopy-assisted transluminal trabeculotomy (GATT) in patients with open-angle glaucoma.Retrospective case series.Eyes of patients >18 years of age who underwent GATT by a single surgeon at Wills Eye Hospital with at least 36 months follow-up.Postoperative changes in outcome measures including intraocular pressure (IOP), medication use and visual acuity were recorded. Failure was defined as IOP > 21mmHg or less than 20% reduction below baseline at any postoperative visit after three months, or need for further glaucoma surgery.Main outcome measures were failure rate, IOP, number of glaucoma medications, and visual acuity at 4 years.59 patients (74 eyes), age 57.1±18.5 years (37.8% female) underwent the GATT procedure. Average follow-up was 47.0±6.7 months (range 35.6 to 76.5 months). Mean IOP was 27.0±10.0 mmHg preoperatively and 14.8±6.5 mmHg at 4 years (45% IOP decrease; P<0.01). Mean number of medications decreased from 3.2±1.0 preoperatively to 2.3±1.0 at 4 years (P< 0.01). The cumulative failure rate at 4 years was 53.9%, and the cumulative reoperation rate was 42.0%. No significant differences between patients with primary open-angle glaucoma and other types of glaucoma were found.GATT can be a safe and effective conjunctival-sparing surgery for in treating various forms of open-angle glaucoma at 4 years.
View details for DOI 10.1016/j.ogla.2023.01.005
View details for PubMedID 36702382
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Epigenetics in glaucoma: a link between DNA methylation and neurodegeneration.
The Journal of clinical investigation
2022; 132 (21)
Abstract
Normal-tension glaucoma is a form of optic nerve degeneration that is characterized by loss of retinal ganglion cells independent of eye pressure elevation. In this issue of the JCI, Pan et al. report the discovery in a Japanese family of a mutation in the METTL23 gene, which encodes a DNA methyltransferase that causes normal-pressure glaucoma in haploinsufficiency. Inherited as an autosomal dominant condition, METTL23 deficiency revealed an important function in the regulation of pS2 and the downstream NF-kappaB signaling pathway, which has previously been linked to glaucomatous optic nerve degeneration. These findings are the first direct link between defective epigenetic regulatory machinery and genetic forms of optic nerve degeneration.
View details for DOI 10.1172/JCI163670
View details for PubMedID 36317630
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Differences in primary cilia amongst retinal ganglion cell subtypes
ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2022
View details for Web of Science ID 000844401302301
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Distribution of prototypical primary cilia markers in subtypes of retinal ganglion cells.
The Journal of comparative neurology
2022
Abstract
Loss of retinal ganglion cells (RGCs) underlies several forms of retinal disease including glaucomatous optic neuropathy, a leading cause of irreversible blindness. Several rare genetic disorders associated with cilia dysfunction have retinal degeneration as a clinical hallmark. Much of the focus of ciliopathy associated blindness is on the connecting cilium of photoreceptors; however, RGCs also possess primary cilia. It is unclear what roles RGC cilia play, what proteins and signaling machinery localize to RGC cilia, or how RGC cilia are differentiated across the subtypes of RGCs. To better understand these questions, we assessed the presence or absence of a prototypical cilia marker Arl13b and a widely distributed neuronal cilia marker AC3 in different subtypes of mouse RGCs. Interestingly, not all RGC subtype cilia are the same and there are significant differences even among these standard cilia markers. Alpha-RGCs positive for osteopontin, calretinin, and SMI32 primarily possess AC3-positive cilia. Directionally selective RGCs that are CART positive or Trhr positive localize either Arl13b or AC3, respectively, in cilia. Intrinsically photosensitive RGCs differentially localize Arl13b and AC3 based on melanopsin expression. Taken together, we characterized the localization of gold standard cilia markers in different subtypes of RGCs and conclude that cilia within RGC subtypes may be differentially organized. Future studies aimed at understanding RGC cilia function will require a fundamental ability to observe the cilia across subtypes as their signaling protein composition is elucidated. A comprehensive understanding of RGC cilia may reveal opportunities to understanding how their dysfunction leads to retinal degeneration.
View details for DOI 10.1002/cne.25326
View details for PubMedID 35434813
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Repair of Tube Erosion by Modifying the Tube Extender
JOURNAL OF GLAUCOMA
2020; 29 (7): 604-606
Abstract
We describe here a case report of a novel technique for tube erosion repair, which modifies and utilizes the commercially available tube extender (Model TE). The modification of the tube extender makes the commercially available tube extender more compact and is useful in cases where conjunctival mobility and space are limited. This debulking of the tube extender may reduce the risk of future tube exposure and dellen formation.
View details for DOI 10.1097/IJG.0000000000001505
View details for Web of Science ID 000559090500025
View details for PubMedID 32251073
View details for PubMedCentralID PMC7337120
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Three-dimensional Neuroretinal Rim Thickness and Visual Fields in Glaucoma: A Broken-stick Model.
Journal of glaucoma
2020; 29 (10): 952-963
Abstract
In open-angle glaucoma, when neuroretinal rim tissue measured by volumetric optical coherence tomography (OCT) scans is below a third of the normal value, visual field (VF) damage becomes detectable.To determine the amount of neuroretinal rim tissue thickness below which VF damage becomes detectable.In a retrospective cross-sectional study, 1 eye per subject (of 57 healthy and 100 open-angle glaucoma patients) at an academic institution had eye examinations, VF testing, spectral-domain OCT retinal nerve fiber layer (RNFL) thickness measurements, and optic nerve volumetric scans. Using custom algorithms, the minimum distance band (MDB) neuroretinal rim thickness was calculated from optic nerve scans. "Broken-stick" regression was performed for estimating both the MDB and RNFL thickness tipping-point thresholds, below which were associated with initial VF defects in the decibel scale. The slopes for the structure-function relationship above and below the thresholds were computed. Smoothing curves of the MDB and RNFL thickness covariates were evaluated to examine the consistency of the independently identified tipping-point pairs.Plots of VF total deviation against MDB thickness revealed plateaus of VF total deviation unrelated to MDB thickness. Below the thresholds, VF total deviation decreased with MDB thickness, with the associated slopes significantly greater than those above the thresholds (P<0.014). Below 31% of global MDB thickness, and 36.8% and 43.6% of superior and inferior MDB thickness, VF damage becomes detectable. The MDB and RNFL tipping points were in good accordance with the correlation of the MDB and RNFL thickness covariates.When neuroretinal rim tissue, characterized by MDB thickness in OCT, is below a third of the normal value, VF damage in the decibel scale becomes detectable.
View details for DOI 10.1097/IJG.0000000000001604
View details for PubMedID 32925518
View details for PubMedCentralID PMC7541591
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Imaging Retinal Ganglion Cell Death and Dysfunction in Glaucoma.
International ophthalmology clinics
2019; 59 (4): 41-54
View details for DOI 10.1097/IIO.0000000000000285
View details for PubMedID 31569133
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Diagnosing Myasthenia Gravis with an Ice Pack
NEW ENGLAND JOURNAL OF MEDICINE
2016; 375 (19): E39
View details for DOI 10.1056/NEJMicm1509523
View details for Web of Science ID 000387534200001
View details for PubMedID 27959645
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Thermosensory processing in the Drosophila brain
NATURE
2015; 519 (7543): 353-+
Abstract
In Drosophila, just as in vertebrates, changes in external temperature are encoded by bidirectional opponent thermoreceptor cells: some cells are excited by warming and inhibited by cooling, whereas others are excited by cooling and inhibited by warming. The central circuits that process these signals are not understood. In Drosophila, a specific brain region receives input from thermoreceptor cells. Here we show that distinct genetically identified projection neurons (PNs) in this brain region are excited by cooling, warming, or both. The PNs excited by cooling receive mainly feed-forward excitation from cool thermoreceptors. In contrast, the PNs excited by warming ('warm-PNs') receive both excitation from warm thermoreceptors and crossover inhibition from cool thermoreceptors through inhibitory interneurons. Notably, this crossover inhibition elicits warming-evoked excitation, because warming suppresses tonic activity in cool thermoreceptors. This in turn disinhibits warm-PNs and sums with feed-forward excitation evoked by warming. Crossover inhibition could cancel non-thermal activity (noise) that is positively correlated among warm and cool thermoreceptor cells, while reinforcing thermal activity which is anti-correlated. Our results show how central circuits can combine signals from bidirectional opponent neurons to construct sensitive and robust neural codes.
View details for DOI 10.1038/nature14170
View details for Web of Science ID 000351171900041
View details for PubMedID 25739502
View details for PubMedCentralID PMC5488797
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Transient and Specific Inactivation of Drosophila Neurons In Vivo Using a Native Ligand-Gated Ion Channel
CURRENT BIOLOGY
2013; 23 (13): 1202-1208
Abstract
A key tool in neuroscience is the ability to transiently inactivate specific neurons on timescales of milliseconds to minutes. In Drosophila, there are two available techniques for accomplishing this (shibire(ts) and halorhodopsin [1-3]), but both have shortcomings [4-9]. Here we describe a complementary technique using a native histamine-gated chloride channel (Ort). Ort is the receptor at the first synapse in the visual system. It forms large-conductance homomeric channels that desensitize only modestly in response to ligand [10]. Many regions of the CNS are devoid of histaminergic neurons [11, 12], raising the possibility that Ort could be used to artificially inactivate specific neurons in these regions. To test this idea, we performed in vivo whole-cell recordings from antennal lobe neurons misexpressing Ort. In these neurons, histamine produced a rapid and reversible drop in input resistance, clamping the membrane potential below spike threshold and virtually abolishing spontaneous and odor-evoked activity. Every neuron type in this brain region could be inactivated in this manner. Neurons that did not misexpress Ort showed negligible responses to histamine. Ort also performed favorably in comparison to the available alternative effector transgenes. Thus, Ort misexpression is a useful tool for probing functional connectivity among Drosophila neurons.
View details for DOI 10.1016/j.cub.2013.05.016
View details for Web of Science ID 000321605600021
View details for PubMedID 23770187
View details for PubMedCentralID PMC3725270
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Glutamate is an inhibitory neurotransmitter in the Drosophila olfactory system
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2013; 110 (25): 10294-10299
Abstract
Glutamatergic neurons are abundant in the Drosophila central nervous system, but their physiological effects are largely unknown. In this study, we investigated the effects of glutamate in the Drosophila antennal lobe, the first relay in the olfactory system and a model circuit for understanding olfactory processing. In the antennal lobe, one-third of local neurons are glutamatergic. Using in vivo whole-cell patch clamp recordings, we found that many glutamatergic local neurons are broadly tuned to odors. Iontophoresed glutamate hyperpolarizes all major cell types in the antennal lobe, and this effect is blocked by picrotoxin or by transgenic RNAi-mediated knockdown of the GluClα gene, which encodes a glutamate-gated chloride channel. Moreover, antennal lobe neurons are inhibited by selective activation of glutamatergic local neurons using a nonnative genetically encoded cation channel. Finally, transgenic knockdown of GluClα in principal neurons disinhibits the odor responses of these neurons. Thus, glutamate acts as an inhibitory neurotransmitter in the antennal lobe, broadly similar to the role of GABA in this circuit. However, because glutamate release is concentrated between glomeruli, whereas GABA release is concentrated within glomeruli, these neurotransmitters may act on different spatial and temporal scales. Thus, the existence of two parallel inhibitory transmitter systems may increase the range and flexibility of synaptic inhibition.
View details for DOI 10.1073/pnas.1220560110
View details for Web of Science ID 000321500200061
View details for PubMedID 23729809
View details for PubMedCentralID PMC3690841
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Organic-inorganic interfaces and spiral growth in nacre
JOURNAL OF THE ROYAL SOCIETY INTERFACE
2009; 6 (33): 367-376
Abstract
Nacre, the crown jewel of natural materials, has been extensively studied owing to its remarkable physical properties for over 160 years. Yet, the precise structural features governing its extraordinary strength and its growth mechanism remain elusive. In this paper, we present a series of observations pertaining to the red abalone (Haliotis rufescens) shell's organic-inorganic interface, organic interlayer morphology and properties, large-area crystal domain orientations and nacre growth. In particular, we describe unique lateral nano-growths and paired screw dislocations in the aragonite layers, and demonstrate that the organic material sandwiched between aragonite platelets consists of multiple organic layers of varying nano-mechanical resilience. Based on these novel observations and analysis, we propose a spiral growth model that accounts for both [001] vertical propagation via helices that surround numerous screw dislocation cores and simultaneous 010 lateral growth of aragonite sheet structure. These new findings may aid in creating novel organic-inorganic micro/nano composites through synthetic or biomineralization pathways.
View details for DOI 10.1098/rsif.2008.0316
View details for Web of Science ID 000264357800004
View details for PubMedID 18753125
View details for PubMedCentralID PMC2572677
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A Microfluidic Chamber for Analysis of Neuron-to-Cell Spread and Axonal Transport of an Alpha-Herpesvirus
PLOS ONE
2008; 3 (6): e2382
Abstract
Alpha-herpesviruses, including herpes simplex virus and pseudorabies virus (PRV), infect the peripheral nervous system (PNS) of their hosts. Here, we describe an in vitro method for studying neuron-to-cell spread of infection as well as viral transport in axons. The method centers on a novel microfluidic chamber system that directs growth of axons into a fluidically isolated environment. The system uses substantially smaller amounts of virus inoculum and media than previous chamber systems and yet offers the flexibility of applying multiple virology and cell biology assays including live-cell optical imaging. Using PRV infection of cultured PNS neurons, we demonstrate that the microfluidic chamber recapitulates all known facets of neuron-to-cell spread demonstrated in animals and other compartmented cell systems.
View details for DOI 10.1371/journal.pone.0002382
View details for Web of Science ID 000263280700003
View details for PubMedID 18560518
View details for PubMedCentralID PMC2426917