Bio

Bio


Dr. Jeffrey Goldberg is Professor and Chair of Ophthalmology at the Byers Eye Institute at Stanford University. His clinical effort is focused on patients in need of medical or surgical intervention for glaucoma and other retinal and optic nerve diseases, as well as cataract. His research is directed at neuroprotection and regeneration of retinal ganglion cells and the optic nerve, a major unmet need in glaucoma and other optic neuropathies, and his laboratory is developing novel stem cell and nanotherapeutics approaches for eye repair.

Dr. Goldberg received his B.S. magna cum laude from Yale University, and his M.D. and Ph.D. from Stanford University where he made significant discoveries about the failure of optic nerve regeneration. He did his clinical training in ophthalmology and then in glaucoma at the Bascom Palmer Eye Institute, and was awarded a fellowship from the Heed Foundation. He was named the 2010 Scientist of the Year by the Hope For Vision foundation, and received the Cogan award from the Association for Research in Vision and Ophthalmology in 2012. He was elected in 2010 to the American Society of Clinical Investigation, an honorary society of physician scientists. He directs an NIH-funded research laboratory and has developed significant expertise with implementing FDA IND clinical trials for optic nerve neuroprotection and regeneration. His goal is to translate scientific discoveries to patient therapies.

Clinical Focus


  • Ophthalmology

Academic Appointments


Administrative Appointments


  • Chair of Ophthlmology, Stanford University (2015 - Present)

Professional Education


  • Fellowship:Bascom Palmer Eye Institute (2010) FL
  • Board Certification: Ophthalmology, American Board of Ophthalmology (2009)
  • Residency:Bascom Palmer Eye Institute (2008) FL
  • Internship:Santa Clara Valley Medical Center (2004) CA
  • Medical Education:Stanford School of Medicine (2003) CA
  • Fellowship, Bascom Palmer Eye Institute, Glaucoma (2010)
  • PhD, Stanford University, Neurosciences (2003)
  • MD, Stanford University, Medicine (2003)

Research & Scholarship

Current Research and Scholarly Interests


Lab research on molecular mechanisms of survival and regeneration in the visual system; retinal development and stem cell biology; nanoparticles and tissue engineering. Clinical trials in imaging, biomarker development, and neuroprotection and vision restoration in glaucoma and other neurodegenerative diseases.

Clinical Trials


  • Study of NT-501 Encapsulated Cell Therapy for Glaucoma Neuroprotection and Vision Restoration Recruiting

    This is a randomized, sham controlled, masked clinical trial of 60 study participants with glaucoma. Participants with a qualifying study eye will be randomized after screening and baseline evaluations to receive the NT-501 encapsulated cell therapy (ECT) implant or a sham surgery (control arm), and no explant will be required. An examination for safety will occur one day and one week following implant and periodically thereafter for 24 months post-implant. Based on the primary analysis of data at 6 months, patients in the control arm may be offered the NT-501 ECT implant at the 12 month time point.

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  • NT-501 CNTF Implant for Glaucoma: Safety, Neuroprotection and Neuroenhancement Not Recruiting

    Ciliary Neurotrophic Factor (CNTF) has been demonstrated in multiple pre-clinical models to enhance survival and regeneration of retinal ganglion cells, the retinal neurons injured in diseases like glaucoma. We hypothesize that CNTF delivery to the human eye will provide neuroprotection (prevent loss of vision) and neuroenhancement (improve vision indices) in glaucoma. Patients in the trial will receive an NT-501 CNTF implant (made by Neurotech) into one eye, and will be carefully followed to evaluate safety and efficacy.

    Stanford is currently not accepting patients for this trial.

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  • Study to Evaluate Safety and Efficacy of rhNGF Eye Drops Solution Versus Vehicle in Patients With Glaucoma Not Recruiting

    An 8 Week phase Ib, monocentric, randomized, double-masked, vehicle controlled, parallel groups, study with a 24 Week follow-up period to evaluate the safety and potential efficacy of a 180 μg/ml recombinant human nerve growth factor (rhNGF) eye drops solution versus vehicle in patients with glaucoma.

    Stanford is currently not accepting patients for this trial.

    View full details

Publications

All Publications


  • Novel Roles and Mechanism for Krüppel-like Factor 16 (KLF16) Regulation of Neurite Outgrowth and Ephrin Receptor A5 (EphA5) Expression in Retinal Ganglion Cells. journal of biological chemistry Wang, J., Galvao, J., Beach, K. M., Luo, W., Urrutia, R. A., Goldberg, J. L., Otteson, D. C. 2016; 291 (35): 18084-18095

    Abstract

    Regenerative medicine holds great promise for the treatment of degenerative retinal disorders. Krüppel-like factors (KLFs) are transcription factors that have recently emerged as key tools in regenerative medicine because some of them can function as epigenetic reprogrammers in stem cell biology. Here, we show that KLF16, one of the least understood members of this family, is a POU4F2 independent transcription factor in retinal ganglion cells (RGCs) as early as embryonic day 15. When overexpressed, KLF16 inhibits RGC neurite outgrowth and enhances RGC growth cone collapse in response to exogenous ephrinA5 ligands. Ephrin/EPH signaling regulates RGC connectivity. The EphA5 promoter contains multiple GC- and GT-rich KLF-binding sites, which, as shown by ChIP-assays, bind KLF16 in vivo In electrophoretic mobility shift assays, KLF16 binds specifically to a single KLF site near the EphA5 transcription start site that is required for KLF16 transactivation. Interestingly, methylation of only six of 98 CpG dinucleotides within the EphA5 promoter blocks its transactivation by KLF16 but enables transactivation by KLF2 and KLF15. These data demonstrate a role for KLF16 in regulation of RGC neurite outgrowth and as a methylation-sensitive transcriptional regulator of EphA5 expression. Together, these data identify differential low level methylation as a novel mechanism for regulating KLF16-mediated EphA5 expression across the retina. Because of the critical role of ephrin/EPH signaling in patterning RGC connectivity, understanding the role of KLFs in regulating neurite outgrowth and Eph receptor expression will be vital for successful restoration of functional vision through optic nerve regenerative therapies.

    View details for DOI 10.1074/jbc.M116.732339

    View details for PubMedID 27402841

  • NEUROREGENERATION. Promoting CNS repair. Science Cameron, E. G., Goldberg, J. L. 2016; 353 (6294): 30-31

    View details for DOI 10.1126/science.aag3327

    View details for PubMedID 27365439

  • Novel Identity and Functional Markers for Human Corneal Endothelial Cells INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE Bartakova, A., Alvarez-Delfin, K., Weisman, A. D., Salero, E., Raffa, G. A., Merkhofer, R. M., Kunzevitzky, N. J., Goldberg, J. L. 2016; 57 (6): 2749-2762

    Abstract

    Human corneal endothelial cell (HCEC) density decreases with age, surgical complications, or disease, leading to vision impairment. Such endothelial dysfunction is an indication for corneal transplantation, although there is a worldwide shortage of transplant-grade tissue. To overcome the current poor donor availability, here we isolate, expand, and characterize HCECs in vitro as a step toward cell therapy.Human corneal endothelial cells were isolated from cadaveric corneas and expanded in vitro. Cell identity was evaluated based on morphology and immunocytochemistry, and gene expression analysis and flow cytometry were used to identify novel HCEC-specific markers. The functional ability of HCEC to form barriers was assessed by transendothelial electrical resistance (TEER) assays.Cultured HCECs demonstrated canonical morphology for up to four passages and later underwent endothelial-to-mesenchymal transition (EnMT). Quality of donor tissue influenced cell measures in culture including proliferation rate. Cultured HCECs expressed identity markers, and microarray analysis revealed novel endothelial-specific markers that were validated by flow cytometry. Finally, canonical HCECs expressed higher levels of CD56, which correlated with higher TEER than fibroblastic HCECs.In vitro expansion of HCECs from cadaveric donor corneas yields functional cells identifiable by morphology and a panel of novel markers. Markers described correlated with function in culture, suggesting a basis for cell therapy for corneal endothelial dysfunction.

    View details for DOI 10.1167/iovs.15-18826

    View details for Web of Science ID 000378041700044

    View details for PubMedID 27196322

  • Ocular Stem Cell Research from Basic Science to Clinical Application: A Report from Zhongshan Ophthalmic Center Ocular Stem Cell Symposium INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Ouyang, H., Goldberg, J. L., Chen, S., Li, W., Xu, G., Li, W., Zhang, K., Nussenblatt, R. B., Liu, Y., Xie, T., Chan, C., Zack, D. J. 2016; 17 (3)

    Abstract

    Stem cells hold promise for treating a wide variety of diseases, including degenerative disorders of the eye. The eye is an ideal organ for stem cell therapy because of its relative immunological privilege, surgical accessibility, and its being a self-contained system. The eye also has many potential target diseases amenable to stem cell-based treatment, such as corneal limbal stem cell deficiency, glaucoma, age-related macular degeneration (AMD), and retinitis pigmentosa (RP). Among them, AMD and glaucoma are the two most common diseases, affecting over 200 million people worldwide. Recent results on the clinical trial of retinal pigment epithelial (RPE) cells from human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) in treating dry AMD and Stargardt's disease in the US, Japan, England, and China have generated great excitement and hope. This marks the beginning of the ocular stem cell therapy era. The recent Zhongshan Ophthalmic Center Ocular Stem Cell Symposium discussed the potential applications of various stem cell types in stem cell-based therapies, drug discoveries and tissue engineering for treating ocular diseases.

    View details for DOI 10.3390/ijms17030415

    View details for Web of Science ID 000373712800084

    View details for PubMedID 27102165

  • 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

  • Control of Retinal Ganglion Cell Positioning and Neurite Growth: Combining 3D Printing with Radial Electrospun Scaffolds TISSUE ENGINEERING PART A Kador, K. E., Grogan, S. P., Dorthe, E. W., Venugopalan, P., Malek, M. F., Goldberg, J. L., D'Lima, D. D. 2016; 22 (3-4): 286-294

    Abstract

    Retinal ganglion cells (RGCs) are responsible for the transfer of signals from the retina to the brain. As part of the central nervous system, RGCs are unable to regenerate following injury, and implanted cells have limited capacity to orient and integrate in vivo. During development, secreted guidance molecules along with signals from extracellular matrix and the vasculature guide cell positioning, for example, around the fovea, and axon outgrowth; however, these changes are temporally regulated and are not the same in the adult. Here, we combine electrospun cell transplantation scaffolds capable of RGC neurite guidance with thermal inkjet 3D cell printing techniques capable of precise positioning of RGCs on the scaffold surface. Optimal printing parameters are developed for viability, electrophysiological function and, neurite pathfinding. Different media, commonly used to promote RGC survival and growth, were tested under varying conditions. When printed in growth media containing both brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF), RGCs maintained survival and normal electrophysiological function, and displayed radial axon outgrowth when printed onto electrospun scaffolds. These results demonstrate that 3D printing technology may be combined with complex electrospun surfaces in the design of future retinal models or therapies.

    View details for DOI 10.1089/ten.tea.2015.0373

    View details for Web of Science ID 000369987900011

    View details for PubMedID 26729061

  • Transplanted neurons integrate into adult retinas and respond to light. Nature communications Venugopalan, P., Wang, Y., Nguyen, T., Huang, A., Muller, K. J., Goldberg, J. L. 2016; 7: 10472-?

    Abstract

    Retinal ganglion cells (RGCs) degenerate in diseases like glaucoma and are not replaced in adult mammals. Here we investigate whether transplanted RGCs can integrate into the mature retina. We have transplanted GFP-labelled RGCs into uninjured rat retinas in vivo by intravitreal injection. Transplanted RGCs acquire the general morphology of endogenous RGCs, with axons orienting towards the optic nerve head of the host retina and dendrites growing into the inner plexiform layer. Preliminary data show in some cases GFP(+) axons extending within the host optic nerves and optic tract, reaching usual synaptic targets in the brain, including the lateral geniculate nucleus and superior colliculus. Electrophysiological recordings from transplanted RGCs demonstrate the cells' electrical excitability and light responses similar to host ON, ON-OFF and OFF RGCs, although less rapid and with greater adaptation. These data present a promising approach to develop cell replacement strategies in diseased retinas with degenerating RGCs.

    View details for DOI 10.1038/ncomms10472

    View details for PubMedID 26843334

  • Muscle A-Kinase Anchoring Protein-a is an Injury-Specific Signaling Scaffold Required for Neurotrophic- and Cyclic Adenosine Monophosphate-Mediated Survival. EBioMedicine Wang, Y., Cameron, E. G., Li, J., Stiles, T. L., Kritzer, M. D., Lodhavia, R., Hertz, J., Nguyen, T., Kapiloff, M. S., Goldberg, J. L. 2015; 2 (12): 1880-1887

    Abstract

    Neurotrophic factor and cAMP-dependent signaling promote the survival and neurite outgrowth of retinal ganglion cells (RGCs) after injury. However, the mechanisms conferring neuroprotection and neuroregeneration downstream to these signals are unclear. We now reveal that the scaffold protein muscle A-kinase anchoring protein-α (mAKAPα) is required for the survival and axon growth of cultured primary RGCs. Although genetic deletion of mAKAPα early in prenatal RGC development did not affect RGC survival into adulthood, nor promoted the death of RGCs in the uninjured adult retina, loss of mAKAPα in the adult increased RGC death after optic nerve crush. Importantly, mAKAPα was required for the neuroprotective effects of brain-derived neurotrophic factor and cyclic adenosine-monophosphate (cAMP) after injury. These results identify mAKAPα as a scaffold for signaling in the stressed neuron that is required for RGC neuroprotection after optic nerve injury.

    View details for DOI 10.1016/j.ebiom.2015.10.025

    View details for PubMedID 26844267

  • In vivo imaging of axonal transport of mitochondria in the diseased and aged mammalian CNS PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Takihara, Y., Inatani, M., Eto, K., Inoue, T., Kreymerman, A., Miyake, S., Ueno, S., Nagaya, M., Nakanishi, A., Iwao, K., Takamura, Y., Sakamoto, H., Satoh, K., Kondo, M., Sakamoto, T., Goldberg, J. L., Nabekura, J., Tanihara, H. 2015; 112 (33): 10515-10520

    Abstract

    The lack of intravital imaging of axonal transport of mitochondria in the mammalian CNS precludes characterization of the dynamics of axonal transport of mitochondria in the diseased and aged mammalian CNS. Glaucoma, the most common neurodegenerative eye disease, is characterized by axon degeneration and the death of retinal ganglion cells (RGCs) and by an age-related increase in incidence. RGC death is hypothesized to result from disturbances in axonal transport and in mitochondrial function. Here we report minimally invasive intravital multiphoton imaging of anesthetized mouse RGCs through the sclera that provides sequential time-lapse images of mitochondria transported in a single axon with submicrometer resolution. Unlike findings from explants, we show that the axonal transport of mitochondria is highly dynamic in the mammalian CNS in vivo under physiological conditions. Furthermore, in the early stage of glaucoma modeled in adult (4-mo-old) mice, the number of transported mitochondria decreases before RGC death, although transport does not shorten. However, with increasing age up to 23-25 mo, mitochondrial transport (duration, distance, and duty cycle) shortens. In axons, mitochondria-free regions increase and lengths of transported mitochondria decrease with aging, although totally organized transport patterns are preserved in old (23- to 25-mo-old) mice. Moreover, axonal transport of mitochondria is more vulnerable to glaucomatous insults in old mice than in adult mice. These mitochondrial changes with aging may underlie the age-related increase in glaucoma incidence. Our method is useful for characterizing the dynamics of axonal transport of mitochondria and may be applied to other submicrometer structures in the diseased and aged mammalian CNS in vivo.

    View details for DOI 10.1073/pnas.1509879112

    View details for Web of Science ID 000359738300093

    View details for PubMedID 26240337

  • Promoting filopodial elongation in neurons by membrane-bound magnetic nanoparticles NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE Pita-Thomas, W., Steketee, M. B., Moysidis, S. N., Thakor, K., Hampton, B., Goldberg, J. L. 2015; 11 (3): 559-567

    Abstract

    Filopodia are 5-10 μm long processes that elongate by actin polymerization, and promote axon growth and guidance by exerting mechanical tension and by molecular signaling. Although axons elongate in response to mechanical tension, the structural and functional effects of tension specifically applied to growth cone filopodia are unknown. Here we developed a strategy to apply tension specifically to retinal ganglion cell (RGC) growth cone filopodia through surface-functionalized, membrane-targeted superparamagnetic iron oxide nanoparticles (SPIONs). When magnetic fields were applied to surface-bound SPIONs, RGC filopodia elongated directionally, contained polymerized actin filaments, and generated retrograde forces, behaving as bona fide filopodia. Data presented here support the premise that mechanical tension induces filopodia growth but counter the hypothesis that filopodial tension directly promotes growth cone advance. Future applications of these approaches may be used to induce sustained forces on multiple filopodia or other subcellular microstructures to study axon growth or cell migration. From the clinical editor: Mechanical tension to the tip of filopodia is known to promote axonal growth. In this article, the authors used superparamagnetic iron oxide nanoparticles (SPIONs) targeted specifically to membrane molecules, then applied external magnetic field to elicit filopodial elongation, which provided a tool to study the role of mechanical forces in filopodia dynamics and function.

    View details for DOI 10.1016/j.nano.2014.11.011

    View details for Web of Science ID 000352081100007

    View details for PubMedID 25596077

  • Regulation of Intrinsic Axon Growth Ability at Retinal Ganglion Cell Growth Cones INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE Steketee, M. B., Oboudiyat, C., Daneman, R., Trakhtenberg, E., Lamoureux, P., Weinstein, J. E., Heidemann, S., Barres, B. A., Goldberg, J. L. 2014; 55 (7): 4369-4377

    Abstract

    Mammalian central nervous system neurons fail to regenerate after injury or disease, in part due to a progressive loss in intrinsic axon growth ability after birth. Whether lost axon growth ability is due to limited growth resources or to changes in the axonal growth cone is unknown.Static and time-lapse images of purified retinal ganglion cells (RGCs) were analyzed for axon growth rate and growth cone morphology and dynamics without treatment and after manipulating Kruppel-like transcription factor (KLF) expression or applying mechanical tension.Retinal ganglion cells undergo a developmental switch in growth cone dynamics that mirrors the decline in postnatal axon growth rates, with increased filopodial adhesion and decreased lamellar protrusion area in postnatal axonal growth cones. Moreover, expressing growth-suppressive KLF4 or growth-enhancing KLF6 transcription factors elicits similar changes in postnatal growth cones that correlate with axon growth rates. Postnatal RGC axon growth rate is not limited by an inability to achieve axon growth rates similar to embryonic RGCs; indeed, postnatal axons support elongation rates up to 100-fold faster than postnatal axonal growth rates. Rather, the intrinsic capacity for rapid axon growth is due to both growth cone pausing and retraction, as well as to a slightly decreased ability to achieve rapid instantaneous rates of forward progression. Finally, we observed that RGC axon and dendrite growth are regulated independently in vitro.Together, these data support the hypothesis that intrinsic axon growth rate is regulated by an axon-specific growth program that differentially regulates growth cone motility.

    View details for DOI 10.1167/iovs.14-13882

    View details for Web of Science ID 000339487000045

    View details for PubMedID 24906860

  • KLF Family Members Regulate Intrinsic Axon Regeneration Ability SCIENCE Moore, D. L., Blackmore, M. G., Hu, Y., Kaestner, K. H., Bixby, J. L., Lemmon, V. P., Goldberg, J. L. 2009; 326 (5950): 298-301

    Abstract

    Neurons in the central nervous system (CNS) lose their ability to regenerate early in development, but the underlying mechanisms are unknown. By screening genes developmentally regulated in retinal ganglion cells (RGCs), we identified Krüppel-like factor-4 (KLF4) as a transcriptional repressor of axon growth in RGCs and other CNS neurons. RGCs lacking KLF4 showed increased axon growth both in vitro and after optic nerve injury in vivo. Related KLF family members suppressed or enhanced axon growth to differing extents, and several growth-suppressive KLFs were up-regulated postnatally, whereas growth-enhancing KLFs were down-regulated. Thus, coordinated activities of different KLFs regulate the regenerative capacity of CNS neurons.

    View details for DOI 10.1126/science.1175737

    View details for Web of Science ID 000270599500045

    View details for PubMedID 19815778

  • Disease gene candidates revealed by expression profiling of retinal ganglion cell development JOURNAL OF NEUROSCIENCE Wang, J. T., Kunzevitzky, N. J., Dugas, J. C., Cameron, M., Barres, B. A., Goldberg, J. L. 2007; 27 (32): 8593-8603

    Abstract

    To what extent do postmitotic neurons regulate gene expression during development or after injury? We took advantage of our ability to highly purify retinal ganglion cells (RGCs) to profile their pattern of gene expression at 13 ages from embryonic day 17 through postnatal day 21. We found that a large proportion of RGC genes are regulated dramatically throughout their postmitotic development, although the genes regulated through development in vivo generally are not regulated similarly by RGCs allowed to age in vitro. Interestingly, we found that genes regulated by developing RGCs are not generally correlated with genes regulated in RGCs stimulated to regenerate their axons. We unexpectedly found three genes associated with glaucoma, optineurin, cochlin, and CYP1B1 (cytochrome P450, family 1, subfamily B, polypeptide 1), previously thought to be primarily expressed in the trabecular meshwork, which are highly expressed by RGCs and regulated through their development. We also identified several other RGC genes that are encoded by loci linked to glaucoma. The expression of glaucoma-linked genes by RGCs suggests that, at least in some cases, RGCs may be directly involved in glaucoma pathogenesis rather than indirectly involved in response to increased intraocular pressure. Consistent with this hypothesis, we found that CYP1B1 overexpression potentiates RGC survival.

    View details for DOI 10.1523/JNEUROSCI.4488-07.2007

    View details for Web of Science ID 000248708400013

    View details for PubMedID 17687037

  • An oligodendrocyte lineage-specific semaphorin, sema5A, inhibits axon growth by retinal ganglion cells JOURNAL OF NEUROSCIENCE Goldberg, J. L., Vargas, M. E., Wang, J. T., Mandemakers, W., Oster, S. F., Sretavan, D. W., Barres, B. A. 2004; 24 (21): 4989-4999

    Abstract

    In the mammalian CNS, glial cells repel axons during development and inhibit axon regeneration after injury. It is unknown whether the same repulsive axon guidance molecules expressed by glia and their precursors during development also play a role in inhibiting regeneration in the injured CNS. Here we investigate whether optic nerve glial cells express semaphorin family members and, if so, whether these semaphorins inhibit axon growth by retinal ganglion cells (RGCs). We show that each optic nerve glial cell type, astrocytes, oligodendrocytes, and their precursor cells, expressed a distinct complement of semaphorins. One of these, sema5A, was expressed only by purified oligodendrocytes and their precursors, but not by astrocytes, and was present in both normal and axotomized optic nerve but not in peripheral nerves. Sema5A induced collapse of RGC growth cones and inhibited RGC axon growth when presented as a substrate in vitro. To determine whether sema5A might contribute to inhibition of axon growth after injury, we studied the ability of RGCs to extend axons when cultured on postnatal day (P) 4, P8, and adult optic nerve explants and found that axon growth was strongly inhibited. Blocking sema5A using a neutralizing antibody significantly increased RGC axon growth on these optic nerve explants. These data support the hypothesis that sema5A expression by oligodendrocyte lineage cells contributes to the glial cues that inhibit CNS regeneration.

    View details for DOI 10.1523/JNEUROSCI.4390-03.2004

    View details for Web of Science ID 000221654400011

    View details for PubMedID 15163691

  • How does an axon grow? GENES & DEVELOPMENT Goldberg, J. L. 2003; 17 (8): 941-958

    View details for DOI 10.1101/gad.1062303

    View details for Web of Science ID 000182361600001

    View details for PubMedID 12704078

  • Amacrine-signaled loss of intrinsic axon growth ability by retinal ganglion cells SCIENCE Goldberg, J. L., Klassen, M. P., Hua, Y., Barres, B. A. 2002; 296 (5574): 1860-1864

    Abstract

    The central nervous system (CNS) loses the ability to regenerate early during development, but it is not known why. The retina has long served as a simple model system for study of CNS regeneration. Here we show that amacrine cells signal neonatal rat retinal ganglion cells (RGCs) to undergo a profound and apparently irreversible loss of intrinsic axon growth ability. Concurrently, retinal maturation triggers RGCs to greatly increase their dendritic growth ability. These results suggest that adult CNS neurons fail to regenerate not only because of CNS glial inhibition but also because of a loss of intrinsic axon growth ability.

    View details for Web of Science ID 000176054300047

    View details for PubMedID 12052959

  • Retinal ganglion cells do not extend axons by default: Promotion by neurotrophic signaling and electrical activity NEURON Goldberg, J. L., Espinosa, J. S., Xu, Y. F., Davidson, N., Kovacs, G. T., Barres, B. A. 2002; 33 (5): 689-702

    Abstract

    We investigate the signaling mechanisms that induce retinal ganglion cell (RGC) axon elongation by asking whether surviving neurons extend axons by default. We show that bcl-2 overexpression is sufficient to keep purified RGCs alive in the absence of any glial or trophic support. The bcl-2-expressing RGCs do not extend axons or dendrites unless signaled to do so by single peptide trophic factors. Axon growth stimulated by peptide trophic factors is remarkably slow but is profoundly potentiated by physiological levels of electrical activity spontaneously generated within embryonic explants or mimicked on a multielectrode silicon chip. These findings demonstrate that these surviving neurons do not constitutively extend axons and provide insight into the signals that may be necessary to promote CNS regeneration.

    View details for Web of Science ID 000174286200006

    View details for PubMedID 11879647

  • EphA receptors regulate growth cone dynamics through the novel guanine nucleotide exchange factor ephexin CELL Shamah, S. M., Lin, M. Z., Goldberg, J. L., Estrach, S., Sahin, M., Hu, L., Bazalakova, M., NEVE, R. L., Corfas, G., Debant, A., Greenberg, M. E. 2001; 105 (2): 233-244

    Abstract

    Eph receptors transduce short-range repulsive signals for axon guidance by modulating actin dynamics within growth cones. We report the cloning and characterization of ephexin, a novel Eph receptor-interacting protein that is a member of the Dbl family of guanine nucleotide exchange factors (GEFs) for Rho GTPases. Ephrin-A stimulation of EphA receptors modulates the activity of ephexin leading to RhoA activation, Cdc42 and Rac1 inhibition, and cell morphology changes. In addition, expression of a mutant form of ephexin in primary neurons interferes with ephrin-A-induced growth cone collapse. The association of ephexin with Eph receptors constitutes a molecular link between Eph receptors and the actin cytoskeleton and provides a novel mechanism for achieving highly localized regulation of growth cone motility.

    View details for Web of Science ID 000168384300010

    View details for PubMedID 11336673

  • The relationship between neuronal survival and regeneration ANNUAL REVIEW OF NEUROSCIENCE Goldberg, J. L., Barres, B. A. 2000; 23: 579-612

    Abstract

    The ability of peripheral nervous system (PNS) but not central nervous system (CNS) neurons to regenerate their axons is a striking peculiarity of higher vertebrates. Much research has focused on the inhibitory signals produced by CNS glia that thwart regenerating axons. Less attention has been paid to the injury-induced loss of trophic stimuli needed to promote the survival and regeneration of axotomized neurons. Could differences in the mechanisms that control CNS and PNS neuronal survival and growth also contribute to the disparity in regenerative capacity? Here we review recent studies concerning the nature of the signals necessary to promote neuronal survival and growth, with an emphasis on their significance to regeneration after CNS injury.

    View details for Web of Science ID 000086730500020

    View details for PubMedID 10845076

  • Neural regeneration: Extending axons from bench to brain CURRENT BIOLOGY Goldberg, J. L., Barres, B. A. 1998; 8 (9): R310-R312

    Abstract

    Many studies have shown that myelin in the central nervous system strongly inhibits the regeneration of axons, so it comes as a surprise to discover that adult neurons transplanted into the brain rapidly extend their axons through myelinated pathways.

    View details for Web of Science ID 000073343100011

    View details for PubMedID 9560333