Bio

Bio


Dr. Liao received her undergraduate degree with high honors from Harvard University in Biochemical Sciences and her M.D., Ph.D. in Neuroscience and Fellowship in Neuro-Ophthalmology from University of California San Francisco Medical Scientist Training Program. Dr. Liao is studying vision problems due to nervous system diseases and their treatment. A major area of research is the understanding and treatment for retinal ganglion cell loss and optic neuropathies like anterior ischemic optic neuropathy, the most common acute optic neuropathy in adults. Her group has evaluated key events following ischemia and identified potential targets and treatment modalities in photochemical thrombosis model of anterior ischemic optic neuropathy. 1) She is studying potential neuroprotective agents that may salvage retinal ganglion cells or optic nerve axons following injury, using in vitro as well as noninvasive, serial in vivo imaging techniques including spectral-domain optical coherence tomography and confocal scanning laser ophthalmoscopy. 2) She is investigating changes in retinal ganglion axons and optic nerve glia after ischemic optic neuropathy, which leads to axonal and somatic degeneration. 3) She is investigating the potential of stem cell therapies in improving visual outcome acutely or chronically. In addition, Dr. Liao is investigating non-invasive measurements of retina and optic nerve, eye movement, visual behavior, and pupillary behavior as biomarkers of disease or treatment efficacy. She is specifically interested in the study of reading, including how neuro-ophthalmic diseases such as vision loss or eye movement disorder such as Parkinson's disease affect this functionally significant daily activity. By recording and studying eye movement abnormalities, Dr. Liao hopes to decipher what contributes to visual dysfunction in different conditions and to devise appropriate treatment.

Clinical Focus


  • Ischemic Optic Neuropathy
  • Stem cell
  • Parkinson's disease and parkinsonism
  • Eye Movement Disorders
  • Diplopia
  • Leber's hereditary optic neuropathy
  • Optic Neuritis and Multiple Sclerosis
  • Stroke
  • Pseudotumor Cerebri
  • Nystagmus
  • Neuro-Ophthalmology
  • Ophthalmology

Academic Appointments


Administrative Appointments


  • Director, Neuro-Ophthalmology (2008 - Present)
  • Director, Stanford Human Ocular Motor Center (2006 - Present)
  • Co-Program Director, Vision Research Training Program (2010 - Present)
  • Associate Director, Research (2008 - Present)

Honors & Awards


  • Dean's Prize in Research, University of California, San Francisco (1992)
  • S. Weir Mitchell Award, American Academy of Neurology (2004)
  • K08 Award, National Institute of Neurological Diseases and Stroke (2003-2008)
  • Career Award in Biomedical Sciences, Burroughs Wellcome Foundation (2005-2014)
  • Grant Award, Stanford University Vice Provost Undergraduate Research Faculty Grant (2010-2012)
  • Young Investigator Award, North American Neuro-Ophthalmology Society (2011)
  • Grant Award, Weston Havens Foundation (2011-2013)
  • Grant Award, Center for Biomedical Imaging at Stanford (2011-2012, 2013-2014)
  • McCormick Faculty Award, Office of Diversity and Leadership (2011-2013)

Boards, Advisory Committees, Professional Organizations


  • Chair, Informatics Committee, North American Neuro-Ophthalmology Society (NANOS) (2015 - Present)
  • Member, Scientific Program Committee, North American Neuro-Ophthalmology Society (NANOS) (2015 - Present)
  • Member, Neuro-Ophthalmology subcommittee of Annual Meeting Program Committee, American Association of Ophthalmology (AAO) (2014 - Present)
  • Member, Research Committee, North American Neuro-Ophthalmology Society (NANOS) (2008 - 2014)
  • Member, Abstract Committee, North American Neuro-Ophthalmology Society (NANOS) (2008 - 2014)

Professional Education


  • Fellowship:Univ of California San Francisco (2006) CA
  • Medical Education:Univ of California San Francisco (1998) CA
  • A.B., Harvard, Biochemical Sciences (1991)
  • Ph.D., UCSF, Neuroscience (1996)
  • Internship:Stanford University School of Medicine (1999) CA
  • Residency:Stanford University School of Medicine (2002) CA
  • Board Certification: Neurology, American Board of Psychiatry and Neurology (2005)

Research & Scholarship

Current Research and Scholarly Interests


Ischemic optic neuropathy
Stem cell transplantation
Optic neuropathy
Optic neuritis
Eye movement disorders
Parkinson's disease
Multiple sclerosis
Traumatic brain injury

Clinical Trials


  • Study of Pasireotide in Patients With Rare Tumors of Neuroendocrine Origin Not Recruiting

    This study will assess the effectiveness and safety of pasireotide long-acting release in patients who have rare tumors of neuroendocrine origin.

    Stanford is currently not accepting patients for this trial. For more information, please contact Hadar Keren-Gill, (650) 724 - 4131.

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  • Phase 2/3, Randomized, Double-Masked, Sham-Controlled Trial of QPI-1007 in Subjects With Acute Nonarteritic Anterior Ischemic Optic Neuropathy (NAION) Recruiting

    This study will determine the effect of QPI-1007 on visual function in subjects with recent-onset NAION and assess the safety and tolerability of intravitreal injections of QPI-1007 in this population. This study will also evaluate the structural changes in the retina following administration of QPI-1007.

    View full details

  • Clinical Study to Investigate the Long-term Safety, Tolerability, and Efficacy of Ponesimod in Patients With Relapsing-remitting Multiple Sclerosis Not Recruiting

    This study is an extension to the study AC-058B201 and will investigate the long-term safety, tolerability and efficacy of ponesimod in patients with relapsing-remitting multiple sclerosis.

    Stanford is currently not accepting patients for this trial. For more information, please contact Angela Campbell, (650) 721-6188.

    View full details

Projects


  • Disease Pathogenesis and Treatment of Anterior Ischemic Optic Neuropathy, Stanford University (9/9/2008 - Present)

    Location

    Stanford, CA

    Collaborators

    • Jeffrey Goldberg, Professor, Stanford
    • Ben Barres, Professor of Neurobiology, of Developmental Biology, of Neurology and, by courtesy, of Ophthalmology, Stanford
    • Marius Wernig, Associate Professor of Pathology and, by courtesy, of Chemical and Systems Biology, Stanford
    • Lawrence Steinman, Professor, Stanford
  • Eye Movement Control and Abnormalities in Neuro-Ophthalmic Conditions, Stanford University (9/9/2006 - Present)

    Location

    Stanford, CA

  • Stanford Football Head Trauma Study (9/1/2012 - Present)

    Location

    Stanford, CA

    Collaborators

    • David Camarillo, Assistant Professor, Stanford
  • Reading Difficulties in Parkinson's Disease (8/1/2015)

    Location

    Palo Alto, CA

    Collaborators

  • Reading Abnormalities in Neuro-Ophthalmic Disorders (8/1/2006)

    Location

    Palo Alto, CA

    Collaborators

    • Gary Steinberg, Professor, Stanford
    • Brian Wandell, Isaac and Madeline Stein Family Professor and Professor, by courtesy, of Electrical Engineering and of Ophthalmology, Stanford
  • Immunology and Vision Loss (8/1/2007)

    Location

    Palo Alto, CA

    Collaborators

  • Human Non-Invasive Imaging and Recording of Brain Behavior (8/1/2006)

    Location

    Palo Alto, CA

    Collaborators

    • Nancy Fischbein, Professor, Stanford
    • Michael Iv, Clinical Instructor, School of Medicine
    • Theodore Leng, Clinical Assistant Professor, School of Medicine
    • Douglas Fredrick, Clinical Professor, School of Medicine
    • Brian Wandell, Isaac and Madeline Stein Family Professor and Professor, by courtesy, of Electrical Engineering and of Ophthalmology, Stanford

Teaching

2016-17 Courses


Graduate and Fellowship Programs


Publications

All Publications


  • Report on the National Eye Institute Audacious Goals Initiative: Regenerating the Optic Nerve. Investigative ophthalmology & visual science Goldberg, J. L., Guido, W., For The Agi Workshop Participants 2016; 57 (3): 1271-1275

    Abstract

    The National Eye Institute (NEI) hosted a workshop on November 19, 2014, as part of the Audacious Goals Initiative (AGI), an NEI-led effort to rapidly expand therapies for eye diseases through coordinated research funding. The central audacious goal aims to demonstrate by 2025 the restoration of usable vision in humans through the regeneration of neurons and neural connections in the eye and visual system. This workshop focused on identifying promising strategies for optic nerve regeneration. Its principal objective was to solicit input on future AGI-related funding announcements, and specifically to ask, where are we now in our scientific progress, and what progress should we reach for in the coming years? A full report was generated as a white paper posted on the NEI Web site; this report summarizes the discussion and outcomes from the meeting and serves as guidance for future funding of research that focuses on optic nerve regeneration.

    View details for DOI 10.1167/iovs.15-18500

    View details for PubMedID 26990163

  • Abnormal Eye Movement Behavior during Reading in Parkinson?s Disease Parkinsonism and Related Disorders Yu, C. Y., Lee, T., Shariati, M., Santini, V., Poston, K., Liao, Y. 2016
  • Optical Coherence Tomography Study of Retinal Changes in Normal Aging and After Ischemia INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE Shariati, M. A., Park, J. H., Liao, Y. J. 2015; 56 (5): 2790-2797

    Abstract

    Age-related thinning of the retinal ganglion cell axons in the nerve fiber layer has been measured in humans using optical coherence tomography (OCT). In this study, we used OCT to measure inner retinal changes in 3-month-, 1-year-, and 2-year-old mice and after experimental anterior ischemic optic neuropathy (AION).We used OCT to quantify retinal thickness in over 200 eyes at different ages before and after a photochemical thrombosis model of AION. The scans were manually or automatically segmented.In normal aging, there was 1.3-?m thinning of the ganglion cell complex (GCC) between 3 months and 1 year (P < 0.0001) and no further thinning at 2 years. In studying age-related inner retinal changes, measurement of the GCC (circular scan) was superior to that of the total retinal thickness (posterior pole scan) despite the need for manual segmentation because it was not contaminated by outer retinal changes. Three weeks after AION, there was 8.9-?m thinning of the GCC (circular scan; P < 0.0001), 50-?m thinning of the optic disc (posterior pole scan; P < 0.0001), and 17-?m thinning of the retina (posterior pole scan; P < 0.0001) in the 3-month-old group. Changes in the older eyes after AION were similar to those of the 3-month-old group.Optical coherence tomography imaging of a large number of eyes showed that, like humans, mice exhibited small, age-related inner retinal thinning. Measurement of the GCC was superior to total retinal thickness in quantifying age-related changes, and both circular and posterior pole scans were useful to track short-term changes after AION.

    View details for DOI 10.1167/iovs.14-15145

    View details for Web of Science ID 000356439200002

    View details for PubMedID 25414186

  • Subretinal fluid is common in experimental non-arteritic anterior ischemic optic neuropathy EYE Yu, C., Ho, J. K., Liao, Y. J. 2014; 28 (12): 1494-1501

    Abstract

    Anterior ischemic optic neuropathy (AION) is an important cause of acute vision loss for which several animal models exist. It has been associated with subretinal fluid in a previous study on patients but not yet so in animal models.A patient presented with acute non-arteritic AION (NAION) and underwent ophthalmic evaluation and testing including fluorescein angiography and spectral-domain optical coherence tomography (SD-OCT). On the basis of the patient's findings, we used SD-OCT circular and volume scans to analyze retinal changes in a murine model of NAION.One week after left eye vision loss, the patient had clinical and imaging findings consistent with NAION. On SD-OCT, there was prominent peripapillary retinal thickening consistent with intra-retinal edema and sub-foveolar fluid. Inspired by the findings in human AION, we looked for similar changes in murine NAION using SD-OCT. The circular scan did not adequately detect the presence of subretinal fluid. Using the 25-line scan, which covered a larger part of the posterior pole, we found that 100% of murine AION resulted in subretinal fluid at day 1. The subretinal fluid resolved by week 1.This study detailed a case of clinical NAION associated with intra-retinal and subretinal fluid. We also found that subretinal fluid was common in murine photochemical thrombosis model of AION and could be found far away from the optic disc.

    View details for DOI 10.1038/eye.2014.220

    View details for Web of Science ID 000346365600014

    View details for PubMedID 25257770

  • Severe, Early Axonal Degeneration Following Experimental Anterior Ischemic Optic Neuropathy INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE Lee, G. H., Stanford, M. P., Shariati, M. A., Ma, J. H., Liao, Y. J. 2014; 55 (11): 7111-7118

    Abstract

    Anterior ischemic optic neuropathy (AION) is the most common acute optic neuropathy in adults older than 50 and leads to axonal degeneration, thinning of the retinal nerve fiber layer and loss of the retinal ganglion cells (RGCs). We used experimental AION model to study early axonal changes following ischemia.We induced optic nerve head ischemia in adult mice using photochemical thrombosis and analyzed retinal changes within 1 week. We used confocal scanning laser ophthalmoscopy (cSLO) and fluorescence microscopy of retinal whole mount preparations to analyze axonal degeneration in Thy1-YFP-H mice and those injected with annexin-V-A488 intravitreally.Three days after AION, morphometric analyses in Thy1-YFP-H mice revealed evidence of early axonal changes, including swollen or branched axonal stumps. There was also a beads-on-a-string appearance of YFP expression. The axonal enlargements occurred at an interval of 17 ▒ 1 ?m or 6 ▒ 0 enlargements/100 ?m. At day 7 after AION, the degenerating intraretinal RGC axons exhibited intense annexin-V-A488 staining (P = 0.002). The annexin-V staining pattern was fragmented, with intersegment interval of 20.1 ▒ 1.4 ?m or 5.8 ▒ 0.4 annexin-V-A488(+) fragments/100 ?m, which were similar to that of degenerating Thy1-YFP(+) axons.Following a photochemical thrombosis model of AION, RGC axons displayed severe degenerative changes within 1 week, suggesting that after ischemia, RGC axons may degenerate in a temporally and spatially distinct fashion from that of the soma. Our findings also further established annexin-V as a useful marker of retinal degeneration because it strongly labeled dying RGC axons.

    View details for DOI 10.1167/iovs.14-14603

    View details for Web of Science ID 000347217300011

    View details for PubMedID 25249599

  • Dose-Response Modeling of the Visual Pathway Tolerance to Single-Fraction and Hypofractionated Stereotactic Radiosurgery SEMINARS IN RADIATION ONCOLOGY Hiniker, S. M., Modlin, L. A., Choi, C. Y., Atalar, B., Seiger, K., Binkley, M. S., Harris, J. P., Liao, Y. J., Fischbein, N., Wang, L., Ho, A., Lo, A., Chang, S. D., Harsh, G. R., Gibbs, I. C., Hancock, S. L., Li, G., Adler, J. R., Soltys, S. G. 2016; 26 (2): 97-104

    Abstract

    Patients with tumors adjacent to the optic nerves and chiasm are frequently not candidates for single-fraction stereotactic radiosurgery (SRS) due to concern for radiation-induced optic neuropathy. However, these patients have been successfully treated with hypofractionated SRS over 2-5 days, though dose constraints have not yet been well defined. We reviewed the literature on optic tolerance to radiation and constructed a dose-response model for visual pathway tolerance to SRS delivered in 1-5 fractions. We analyzed optic nerve and chiasm dose-volume histogram (DVH) data from perioptic tumors, defined as those within 3mm of the optic nerves or chiasm, treated with SRS from 2000-2013 at our institution. Tumors with subsequent local progression were excluded from the primary analysis of vision outcome. A total of 262 evaluable cases (26 with malignant and 236 with benign tumors) with visual field and clinical outcomes were analyzed. Median patient follow-up was 37 months (range: 2-142 months). The median number of fractions was 3 (1 fraction n = 47, 2 fraction n = 28, 3 fraction n = 111, 4 fraction n = 10, and 5 fraction n = 66); doses were converted to 3-fraction equivalent doses with the linear quadratic model using ?/? = 2Gy prior to modeling. Optic structure dose parameters analyzed included Dmin, Dmedian, Dmean, Dmax, V30Gy, V25Gy, V20Gy, V15Gy, V10Gy, V5Gy, D50%, D10%, D5%, D1%, D1cc, D0.50cc, D0.25cc, D0.20cc, D0.10cc, D0.05cc, D0.03cc. From the plan DVHs, a maximum-likelihood parameter fitting of the probit dose-response model was performed using DVH Evaluator software. The 68% CIs, corresponding to one standard deviation, were calculated using the profile likelihood method. Of the 262 analyzed, 2 (0.8%) patients experienced common terminology criteria for adverse events grade 4 vision loss in one eye, defined as vision of 20/200 or worse in the affected eye. One of these patients had received 2 previous courses of radiotherapy to the optic structures. Both cases were meningiomas treated with 25Gy in 5 fractions, with a 3-fraction equivalent optic nerve Dmax of 19.2 and 22.2Gy. Fitting these data to a probit dose-response model enabled risk estimates to be made for these previously unvalidated optic pathway constraints: the Dmax limits of 12Gy in 1 fraction from QUANTEC, 19.5Gy in 3 fractions from Timmerman 2008, and 25Gy in 5 fractions from AAPM Task Group 101 all had less than 1% risk. In 262 patients with perioptic tumors treated with SRS, we found a risk of optic complications of less than 1%. These data support previously unvalidated estimates as safe guidelines, which may in fact underestimate the tolerance of the optic structures, particularly in patients without prior radiation. Further investigation would refine the estimated normal tissue complication probability for SRS near the optic apparatus.

    View details for DOI 10.1016/j.semradonc.2015.11.008

    View details for Web of Science ID 000373242700003

    View details for PubMedID 27000505

  • Giant Cell Arteritis: From Pathogenesis to Therapeutic Management. Current treatment options in rheumatology Watanabe, R., Goronzy, J. J., Berry, G., Liao, Y. J., Weyand, C. M. 2016; 2 (2): 126-137

    View details for DOI 10.1007/s40674-016-0043-x

    View details for PubMedID 27298757

  • Accessory lateral rectus in a patient with normal ocular motor control. Journal of neuro-ophthalmology Liao, Y. J., Hwang, J. J. 2014; 34 (2): 153-154

    Abstract

    : Although supernumerary extraocular muscles are common in monkeys and other species, they are relatively rare in humans and typically are noted in the context of childhood strabismus. We present a case of an incidentally found unilateral accessory lateral rectus muscle in a 51-year-old woman with normal ocular motor control. In this patient, the accessory lateral rectus was approximately 10% the size of a normally sized lateral rectus muscle. It originated from the orbital apex, traveled between the optic nerve and the lateral rectus and attached to the superolateral aspect of the globe. This unique case demonstrates that accessory lateral rectus in humans may have no impact on eye movement and ocular alignment.

    View details for DOI 10.1097/WNO.0000000000000109

    View details for PubMedID 24796602

  • Non-Surgical Treatment for Racemic Neurocysticercosis with Compression of the Optic Nerve Journal of Spine and Neurosurgery Moreno, M., Bui, T., Agarwal, M., Nitta, R., Liao, Y. J., Li, G. 2014
  • Extreme Tolerance of the Optic Nerve to Ionizing Radiation: A Case Report Revealing the Role of the Dose-Volume Effect Cureus Adler, J. R., Murovic, J., Liao, Y. J., Shuer, L. M. 2014
  • Optical Coherence Tomography Study of Experimental Anterior Ischemic Optic Neuropathy and Histologic Confirmation INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE Ho, J. K., Stanford, M. P., Shariati, M. A., Dalal, R., Liao, Y. J. 2013; 54 (9): 5981-5988

    Abstract

    The optic nerve is part of the central nervous system, and interruption of this pathway due to ischemia typically results in optic atrophy and loss of retinal ganglion cells (RGCs). In this study, we assessed in vivo retinal changes following murine anterior ischemic optic neuropathy (AION) using spectral-domain optical coherence tomography (SD-OCT) and compared these anatomic measurements to that of histology.We induced ischemia at the optic disc via laser-activated photochemical thrombosis, performed serial SD-OCT and manual segmentation of the retinal layers to measure the ganglion cell complex (GCC) and total retinal thickness, and correlated these measurements with that of histology.There was impaired perfusion and leakage at the optic disc on fluorescein angiography immediately after AION and severe swelling and distortion of the peri-papillary retina on day-1. We used SD-OCT to quantify the changes in retinal thickness following experimental AION, which revealed significant thickening of the GCC on day-1 after ischemia followed by gradual thinning that plateaued by week-3. Thickness of the peri-papillary sensory retina was also increased on day-1 and thinned chronically. This pattern of acute retinal swelling and chronic thinning on SD-OCT correlated well with changes seen in histology and corresponded to loss of retinal ganglion layer cells after ischemia.This is the first serial SD-OCT quantification of acute and chronic changes following experimental AION, which revealed changes in the ganglion cell complex similar to that of human AION, but over a time frame of weeks rather than months.

    View details for DOI 10.1167/iovs.13-12419

    View details for Web of Science ID 000325169500008

    View details for PubMedID 23887804

  • Treatment of Anterior Ischemic Optic Neuropathy: Clues from the Bench Taiwan Journal of Ophthalmology Liao, Y. J., Hwang, J. J. 2013
  • Traumatic air bag maculopathy Archive of Ophthalmology Kung, J., Leung, L., Leng, T., Liao, Y. J. 2013; 131 (5)
  • The Immunopathology of Giant Cell Arteritis: Diagnostic and Therapeutic Implications JOURNAL OF NEURO-OPHTHALMOLOGY Weyand, C. M., Liao, Y. J., Goronzy, J. J. 2012; 32 (3): 259-265

    Abstract

    Giant cell arteritis (GCA) is an important cause of preventable blindness, most commonly due to anterior ischemic optic neuropathy. Ischemic tissue injury is the end result of a process that begins within the walls of susceptible arteries in which local dendritic cells (DCs) recruit and activate CD4 T cells that, in turn, direct the activity of effector macrophages. In response to the immune attack, the blood vessel forms lumen-stenosing intima. Multiple cascades of excessive T-cell reactivity contribute to the autoimmune features of giant cell arteritis with TH1 and TH17 immunity responsible for the early phase and TH1 immunity promoting chronic-smoldering inflammation. These cascades are only partially overlapping, supporting the concept that a multitude of instigators induce and sustain vascular inflammation. The artery actively participates in the abnormal immune response through endogenous immune sentinels, so-called vascular DCs embedded in the adventitia. Advancing age, the strongest of all risk factors for GCA, contributes to both, the dysfunction of the immune system and the vascular system. Expansion of the therapeutic armamentarium for GCA needs to focus on approaches that mitigate the impact of the aging artery and adapt to the needs of the immunosenescent host.

    View details for DOI 10.1097/WNO.0b013e318268aa9b

    View details for Web of Science ID 000308187800018

    View details for PubMedID 22914691

  • Plasticity and Stability of the Visual System in Human Achiasma NEURON Hoffmann, M. B., Kaule, F. R., Levin, N., Masuda, Y., Kumar, A., Gottlob, I., Horiguchi, H., Dougherty, R. F., Stadler, J., Wolynski, B., Speck, O., Kanowski, M., Liao, Y. J., Wandell, B. A., Dumoulin, S. O. 2012; 75 (3): 393-401

    Abstract

    The absence of the optic chiasm is an extraordinary and extreme abnormality in the nervous system. The abnormality produces highly atypical functional responses in the cortex, including overlapping hemifield representations and bilateral population receptive fields in both striate and extrastriate visual cortex. Even in the presence of these large functional abnormalities, the effect on visual perception and daily life is not easily detected. Here, we demonstrate that in two achiasmic humans the gross topography of the geniculostriate and occipital callosal connections remains largely unaltered. We conclude that visual function is preserved by reorganization of intracortical connections instead of large-scale reorganizations of the visual cortex. Thus, developmental mechanisms of local wiring within cortical maps compensate for the improper gross wiring to preserve function in human achiasma.

    View details for DOI 10.1016/j.neuron.2012.05.026

    View details for Web of Science ID 000307417700007

    View details for PubMedID 22884323

  • Junctional Visual Field Loss in a Case of Wyburn-Mason Syndrome JOURNAL OF NEURO-OPHTHALMOLOGY Liu, A., Chen, Y., Chang, S., Liao, Y. J. 2012; 32 (1): 42-44

    Abstract

    A previously healthy girl failed a routine eye screening at the age of 6 years. Her visual fields showed generalized depression in the right eye and a superotemporal defect in the left eye, consistent with a junctional scotoma. Funduscopic examination and fluorescein angiography revealed markedly dilated tortuous vascular loops with arteriovenous communications consistent with retinal arteriovenous malformations (AVMs). MRI of the brain and cerebral angiography demonstrated right ophthalmic and right thalamic AVMs, with compression and atrophy of the right optic chiasm. This represents a case of Wyburn-Mason syndrome with a junctional scotoma.

    View details for DOI 10.1097/WNO.0b013e31821aeefb

    View details for Web of Science ID 000300607000009

    View details for PubMedID 21613961

  • Functional rescue of experimental ischemic optic neuropathy with alpha B-crystallin EYE Pangratz-Fuehrer, S., Kaur, K., Ousman, S. S., Steinman, L., Liao, Y. J. 2011; 25 (6): 809-817

    Abstract

    Anterior ischemic optic neuropathy (AION) is an important cause of acute vision loss in adults, and there is no effective treatment. We studied early changes following experimental AION and tested the benefit of a potential treatment.Materials andWe induced experimental AION in adult mice and tested the effects of short-term (daily for 3 days) and long-term (every other day for 3 weeks) ?B-crystallin (?BC) treatment using histological and serial intracranial flash visual evoked potential recordings.One day after experimental AION, there was swelling at the optic nerve (ON) head and increased expression of ?BC, a small heat shock protein important in ischemia and inflammation. This upregulation coincided with microglial and astrocytic activation. Our hypothesis was that ?BC may be part of the endogenous protective mechanism against injury, thus we tested the effects of ?BC on experimental AION. Daily intraveneous or intravitreal ?BC injections did not improve visual evoked potential amplitude or latency at days 1-2. However, ?BC treatment decreased swelling and dampened the microglial and astrocytic activation on day 3. Longer treatment with intravenous ?BC led to acceleration of visual evoked potential latency over 3 weeks, without improving amplitude. This latency acceleration did not correlate with increased retinal ganglion cell survival but did correlate with complete rescue of the ON oligodendrocytes, which are important for myelination.We identified ?BC as an early marker following experimental AION. Treatment with ?BC enhanced this endogenous, post-ischemic response by decreasing microglial activation and promoting ON oligodendrocyte survival.

    View details for DOI 10.1038/eye.2011.42

    View details for Web of Science ID 000291430100020

    View details for PubMedID 21475310

  • Dorsolateral Midbrain MRI Abnormalities and Ocular Motor Deficits Following Cytarabine-Based Chemotherapy for Acute Myelogenous Leukemia JOURNAL OF NEURO-OPHTHALMOLOGY Doan, T., Lacayo, N., Fisher, P. G., Liao, Y. J. 2011; 31 (1): 52-53

    View details for DOI 10.1097/WNO.0b013e3181e91174

    View details for Web of Science ID 000287238700013

    View details for PubMedID 20881617

  • Giant cell arteritis: immune and vascular aging as disease risk factors ARTHRITIS RESEARCH & THERAPY Mohan, S. V., Liao, Y. J., Kim, J. W., Goronzy, J. J., Weyand, C. M. 2011; 13 (4)

    Abstract

    Susceptibility for giant cell arteritis increases with chronological age, in parallel with age-related restructuring of the immune system and age-induced remodeling of the vascular wall. Immunosenescence results in shrinkage of the na´ve T-cell pool, contraction of T-cell diversity, and impairment of innate immunity. Aging of immunocompetent cells forces the host to take alternative routes for protective immunity and confers risk for pathogenic immunity that causes chronic inflammatory tissue damage. Dwindling immunocompetence is particularly relevant as the aging host is forced to cope with an ever growing infectious load. Immunosenescence coincides with vascular aging during which the arterial wall undergoes dramatic structural changes and medium and large arteries lose their pliability and elasticity. On the molecular level, elastic fibers deteriorate and matrix proteins accumulate biochemical modifications. Thus, the aging process impacts the two major biologic systems that liaise to promote giant cell arteritis; the immune system and the vessel wall niche.

    View details for DOI 10.1186/ar3358

    View details for Web of Science ID 000297150200044

    View details for PubMedID 21861860

  • Congenital Achiasma and See-Saw Nystagmus in VACTERL Syndrome JOURNAL OF NEURO-OPHTHALMOLOGY Prakash, S., Dumoulin, S. O., Fischbein, N., Wandell, B. A., Liao, Y. J. 2010; 30 (1): 45-48

    Abstract

    A 29-year-old man with vertebral defects, anal atresia, cardiac defects, tracheoesophageal fistula, renal defects, and limb defects (VACTERL) presented with headache, photophobia, and worsening nystagmus. He had near-normal visual acuity and visual fields, absent stereopsis, and see-saw nystagmus. Brain MRI revealed a thin remnant of the optic chiasm but normal-sized optic nerves. Functional MRI during monocular visual stimulation demonstrated non-crossing of the visual evoked responses in the occipital cortex, confirming achiasma. These findings have not previously been reported in VACTERL.

    View details for DOI 10.1097/WNO.0b013e3181c28fc0

    View details for Web of Science ID 000275061500012

    View details for PubMedID 20182207

  • Cytomegalovirus Infection with MRI Signal Abnormalities Affecting the Optic Nerves, Optic Chiasm, and Optic Tracts JOURNAL OF NEURO-OPHTHALMOLOGY Pershing, S., Dunn, J., Khan, A., Liao, Y. J. 2009; 29 (3): 223-226

    Abstract

    A 49-year-old woman who had been immunosuppressed after a renal transplant developed bilateral severe visual loss. Visual acuities were finger counting and hand movements in the two eyes. Both optic nerves were pale. There were no other ophthalmic abnormalities. Brain MRI disclosed marked signal abnormalities involving the optic nerves, optic chiasm, and optic tracts. Cerebrospinal fluid polymerase chain reaction (PCR) was positive for cytomegalovirus. Treatment did not restore vision. Such extensive clinical and imaging involvement of the anterior visual pathway, which has been previously reported with other herpes viruses, illustrates the propensity for this family of viruses to track along axons.

    View details for Web of Science ID 000270048700011

    View details for PubMedID 19726946

  • Genetic and acquired neural diseases involving voltage-gated calcium channels Tsien, R. W., Barrett, C. F., Safa, P., Chen, Y., Boyden, E. S., Liao, Y. J. ROCKEFELLER UNIV PRESS. 2008: 22A-23A
  • Anti-Ca2+ channel antibody attenuates Ca2+ currents and mimics cerebellar ataxia in vivo PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Liao, Y. J., Safa, P., Chen, Y., Sobel, R. A., Boyden, E. S., Tsien, R. W. 2008; 105 (7): 2705-2710

    Abstract

    Voltage-gated Ca(2+) channels (VGCCs) are membrane proteins that determine the activity and survival of neurons, and mutations in the P/Q-type VGCCs are known to cause cerebellar ataxia. VGCC dysfunction may also underlie acquired peripheral and central nervous system diseases associated with small-cell lung cancer, including Lambert-Eaton myasthenic syndrome (LEMS) and paraneoplastic cerebellar ataxia (PCA). The pathogenic role of anti-VGCC antibody in LEMS is well established. Although anti-VGCC antibody is also found in a significant fraction of PCA patients, its contribution to PCA is unclear. Using a polyclonal peptide antibody against a major immunogenic region in P/Q-type VGCCs (the extracellular Domain-III S5-S6 loop), we demonstrated that such antibody was sufficient to inhibit VGCC function in neuronal and recombinant VGCCs, alter cerebellar synaptic transmission, and confer the phenotype of cerebellar ataxia. Our data support the hypothesis that anti-VGCC antibody may play a significant role in the pathogenesis of cerebellar dysfunction in PCA.

    View details for DOI 10.1073/pnas.0710771105

    View details for Web of Science ID 000253469900081

    View details for PubMedID 18272482

  • Visual field maps in a subject without an optic chiasm Dumoulin, S. O., Masuda, Y., Horiguchi, H., Dougherty, R. F., Prakash, S., Liao, Y. J., WANDELL, A. PION LTD. 2008: 44-44
  • Intracranial pressure returns to normal about a month after stopping tetracycline antibiotics ARCHIVES OF OPHTHALMOLOGY Winn, B. J., Liao, Y. J., Horton, J. C. 2007; 125 (8): 1137-1138

    View details for Web of Science ID 000248590600026

    View details for PubMedID 17698769

  • Intracranial hypotension caused by leakage of cerebrospinal fluid from the thecal sac after lumboperitoneal shunt placement JOURNAL OF NEUROSURGERY Liao, Y. J., Dillon, W. P., Chin, C. T., Mcderimott, M. W., Horton, J. H. 2007; 107 (1): 173-177

    Abstract

    The authors describe a newly recognized complication of lumboperitoneal (LP) shunt placement, namely, intracranial hypotension from leakage of cerebrospinal fluid (CSF) through a defect in the lumbar dura created by the shunt catheter. They report on a 47-year-old obese woman with idiopathic intracranial hypertension who underwent routine placement of an LP shunt. Following surgery, her headache became worse. Two radionuclide shunt studies showed no anterograde tracer flow, suggesting either obstruction or a leak. After shunt reservoir manometry indicated low pressure, spinal magnetic resonance (MR) imaging was performed. The MR images revealed a CSF leak from the lumbar thecal sac. A computed tomography (CT) myelogram, performed by injection into the shunt reservoir, confirmed the presence of a leak by showing extravasation of contrast agent into the epidural space. The patient was treated by application of a CT-guided blood patch at the leak site. Catheter-associated CSF leak is an unusual cause of intracranial hypotension that can occur following LP shunt placement. This case report outlines the clinical features of this condition, documents the neuroradiological findings, and demonstrates successful treatment with a blood patch.

    View details for DOI 10.3171/JNS-07/07/0173

    View details for Web of Science ID 000247799900026

    View details for PubMedID 17639890

  • Isolated sixth cranial nerve aplasia visualized with fast imaging employing steady-state acquisition (FIESTA) MRI JOURNAL OF NEURO-OPHTHALMOLOGY Pilyugina, S. A., Fischbein, N. J., Liao, Y. J., McCulley, T. J. 2007; 27 (2): 127-128

    Abstract

    An otherwise healthy 12-month-old girl presented for evaluation of reduced abduction of the left eye detected at 6 months of age. The remainder of the examination was unremarkable. A special MRI sequence-fast imaging employing steady-state acquisition (FIESTA)-visualized the right but not the left sixth nerve cisternal segment. This is the first reported use of the MRI FIESTA sequence to diagnose aplasia of the sixth cranial nerve.

    View details for Web of Science ID 000247021200011

    View details for PubMedID 17548999

  • An approach to critically ill patients in coma WESTERN JOURNAL OF MEDICINE Liao, Y. J., So, Y. T. 2002; 176 (3): 184-187

    View details for Web of Science ID 000179442400012

    View details for PubMedID 12016243

  • Normal cerebellar development but susceptibility to seizures in mice lacking G protein-coupled, inwardly rectifying K+ channel GIRK2 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Signorini, S., Liao, Y. J., Duncan, S. A., Jan, L. Y., Stoffel, M. 1997; 94 (3): 923-927

    Abstract

    G protein-gated, inwardly rectifying K+ channels (GIRK) are effectors of G protein-coupled receptors for neurotransmitters and hormones and may play an important role in the regulation of neuronal excitability. GIRK channels may be important in neurodevelopment, as suggested by the recent finding that a point mutation in the pore region of GIRK2 (G156S) is responsible for the weaver (wv) phenotype. The GIRK2 G156S gene gives rise to channels that exhibit a loss of K+ selectivity and may also exert dominant-negative effects on G(betagamma)-activated K+ currents. To investigate the physiological role of GIRK2, we generated mutant mice lacking GIRK2. Unlike wv/wv mutant mice, GIRK2 -/- mice are morphologically indistinguishable from wild-type mice, suggesting that the wv phenotype is likely due to abnormal GIRK2 function. Like wv/wv mice, GIRK2 -/- mice have much reduced GIRK1 expression in the brain. They also develop spontaneous seizures and are more susceptible to pharmacologically induced seizures using a gamma-aminobutyric acid antagonist. Moreover, wv/- mice exhibit much milder cerebellar abnormalities than wv/wv mice, indicating a dosage effect of the GIRK2 G156S mutation. Our results indicate that the weaver phenotypes arise from a gain-of-function mutation of GIRK2 and that GIRK1 and GIRK2 are important mediators of neuronal excitability in vivo.

    View details for Web of Science ID A1997WG23400028

    View details for PubMedID 9023358

  • Heteromultimerization of G-protein-gated inwardly rectifying K+ channel proteins GIRK1 and GIRK2 and their altered expression in weaver brain JOURNAL OF NEUROSCIENCE Liao, Y. J., Jan, Y. N., Jan, L. Y. 1996; 16 (22): 7137-7150

    Abstract

    The weaver (wv) gene (GIRK2) is a member of the G-protein-gated inwardly rectifying potassium (GIRK) channel family, known effectors in the signal transduction pathway of neurotransmitters such as acetylcholine, dopamine, opioid peptides, and substance P in modulation of neurotransmitter release and neuronal excitability. GIRK2 immunoreactivity is found in but not limited to brain regions known to be affected in wv mice, such as the cerebellar granule cells and dopaminergic neurons in the substantia nigra pars compacta. It is also observed in the ventral tegmental area, hippocampus, cerebral cortex, and thalamus. GIRK2 and GIRK1, a related family member, have overlapping yet distinct distributions in rat and mouse brains. In regions where both channel proteins are expressed, such as the cerebral cortex, hippocampus, and cerebellum, they can be co-immunoprecipitated, indicating that they interact to form heteromeric channels in vivo. In the brain of the wv mouse, GIRK2 expression is decreased dramatically. In regions where GIRK1 and GIRK2 distributions overlap, both GIRK1 and GIRK2 expressions are severely disrupted, probably because of their co-assembly. The expression patterns of these GIRK channel subunits provide a basis for consideration of the machinery for neuronal signaling as well as the differential effects of the wv mutation in various neurons.

    View details for Web of Science ID A1996VR62100005

    View details for PubMedID 8929423

  • Functional effects of the mouse weaver mutation on g protein-gated inwardly rectifying K+ channels NEURON Slesinger, P. A., Patil, N., Liao, Y. J., Jan, Y. N., Jan, L. Y., Cox, D. R. 1996; 16 (2): 321-331

    Abstract

    The weaver mutation corresponds to a substitution of glycine to serine in the H5 region of a G protein-gated inwardly rectifying K+ channel gene (GIRK2). By studying mutant GIRK2 weaver homomultimeric channels and heteromultimeric channels comprised of GIRK2 weaver and GIRK1 in Xenopus oocytes, we found that GIRK2 weaver homomultimeric channels lose their selectivity for K+ ions, giving rise to inappropriate receptor-activated and basally active Na+ currents, whereas heteromultimers of GIRK2 weaver and GIRK1 appeared to have reduced current. Immunohistochemical localization indicates that GIRK2 and GIRK1 proteins are expressed in the cerebellar neurons of mice at postnatal day 4, at a time when these neurons normally undergo differentiation. Thus, the aberrant behavior of mutant GIRK2 weaver channels could affect the development of weaver mice in at least two distinct ways.

    View details for Web of Science ID A1996TW95700012

    View details for PubMedID 8789947

  • DISTINCT MORPHOGENETIC FUNCTIONS OF SIMILAR SMALL GTPASES - DROSOPHILA DRAC1 IS INVOLVED IN AXONAL OUTGROWTH AND MYOBLAST FUSION GENES & DEVELOPMENT Luo, L. Q., Liao, Y. J., Jan, L. Y., Jan, Y. N. 1994; 8 (15): 1787-1802

    Abstract

    The small GTPases of the Rac/Rho/Cdc42 subfamily are implicated in actin cytoskeleton-membrane interaction in mammalian cells and budding yeast. The in vivo functions of these GTPases in multicellular organisms are not known. We have cloned Drosophila homologs of rac and CDC42, Drac1, and Dcdc42. They share 70% amino acid sequence identity with each other, and both are highly expressed in the nervous system and mesoderm during neuronal and muscle differentiation, respectively. We expressed putative constitutively active and dominant-negative Drac1 proteins in these tissues. When expressed in neurons, Drac1 mutant proteins cause axon outgrowth defects in peripheral neurons without affecting dendrites. When expressed in muscle precursors, they cause complete failure of, or abnormality in, myoblast fusion. Expressions of analogous mutant Dcdc42 proteins cause qualitatively distinct morphological defects, suggesting that similar GTPases in the same subfamily have unique roles in morphogenesis.

    View details for Web of Science ID A1994PB10400005

    View details for PubMedID 7958857

  • PRESYNAPTIC A-CURRENT BASED ON HETEROMULTIMERIC K+ CHANNELS DETECTED IN-VIVO NATURE Sheng, M., Liao, Y. J., Jan, Y. N., Jan, L. Y. 1993; 365 (6441): 72-75

    Abstract

    A wide variety of voltage-gated K+ channels are involved in the regulation of neuronal excitability and synaptic transmission. Their heterogeneity arises in part from the large number of genes encoding different K+ channel subunits (reviewed in ref. 1). In addition, heterologous expression studies indicate that assembly of distinct subunits into heteromultimeric channels may contribute further to K+ channel diversity. A question has been whether heteromeric K+ channels actually form in vivo, and if so, whether specific combinations of subunits could account for major K+ currents identified in neurons. We present here biochemical evidence that Kv1.4 and Kv1.2, two K+ channel subunits of the Shaker subfamily, co-assemble in rat brain. The Kv1.4/Kv1.2 heteromultimer combines features of both parent subunits, resulting in an A-type K+ channel. Immunocytochemical evidence suggests that the heteromultimers are localized in axons and nerve terminals. We propose that Kv1.4/Kv1.2 heteromultimers may form the molecular basis of a presynaptic A-type K+ channel involved in the regulation of neurotransmitter release.

    View details for Web of Science ID A1993LV64600057

    View details for PubMedID 8361540

  • HUMAN FETAL LIVER GAMMA/DELTA T-CELLS PREDOMINANTLY USE UNUSUAL REARRANGEMENTS OF THE T-CELL RECEPTOR DELTA-LOCI AND GAMMA-LOCI EXPRESSED ON BOTH CD4+CD8- AND CD4-CD8- GAMMA/DELTA T-CELLS JOURNAL OF EXPERIMENTAL MEDICINE Wucherpfennig, K. W., Liao, Y. J., Prendergast, M., Prendergast, J., Hafler, D. A., STROMINGER, J. L. 1993; 177 (2): 425-432

    Abstract

    Substantial numbers of both alpha/beta and gamma/delta T cells are present in human fetal liver, which suggests a role of the fetal liver in T cell development. The diversity of fetal liver T cell receptor (TCR) gamma and delta chain rearrangements was examined among both CD4+CD8- and CD4-CD8- gamma/delta T cell clones. In addition, TCR delta chain transcripts from three fetal livers were sequenced after polymerase chain reaction amplification of TCR delta chains with V delta 1 or V delta 2 rearrangements. Five of six fetal liver gamma/delta T cell clones had a V delta 2-D delta 3-J delta 3 gene rearrangement with limited junctional diversity; three of these clones had an unusual CD4+CD8- phenotype. V delta 2-D delta 3-J delta 3 gene rearrangements were also common among both in-frame and out-of-frame transcripts from three fetal livers, indicating that they are the result of an ordered rearrangement process. TCR gamma chain sequences of the fetal liver gamma/delta T cell clones revealed V gamma 1-J gamma 2.3, V gamma 2-J gamma 1.2, and V gamma 3-J gamma 1.1 rearrangements with minimal incorporation of template-independent N region nucleotides. TCR gamma chain rearrangements found in these fetal liver T cell clones were different from those that have been observed among early thymic gamma/delta T cell populations, while similar TCR delta chain rearrangements are found among gamma/delta T cells from both sites. These data demonstrate that the fetal liver harbors gamma/delta T cell populations distinct from those found in the fetal thymus, suggesting that the fetal liver is a site of gamma/delta T cell development in humans. These unusual T cell populations may serve a specific function in the fetal immune system.

    View details for Web of Science ID A1993KJ44100019

    View details for PubMedID 8093893

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