About

Wonkyu “Daniel” Ju, M.S., Ph.D., is the Principal Investigator and Professor holding the Hanna and Mark Gleiberman Chancellor’s Endowed Chair in Glaucoma Research at the Viterbi Family Vision Research Center and Gleiberman Center for Glaucoma Research. He is affiliated with the Viterbi Family Department of Ophthalmology and Shiley Eye Institute at the University of California, San Diego. Additionally, he serves as an Affiliate Professor in the Shu Chien-Gene Lay Department of Bioengineering at UC San Diego and is a member of the Biophotonics Technology Center (BTC) within the Institute of Engineering in Medicine at the same institution. His professional roles indicate a focus on glaucoma research and vision science, integrating ophthalmology with bioengineering and biophotonics technologies.

Research topics

• Neuroscience
• Medicine
• Biology
• Cell biology
• Internal medicine
• Endocrinology
• Genetics
• Immunology
• Pathology
• Biochemistry

Selected publications

• Restoring AIBP expression in the retina provides neuroprotection in glaucoma

  Molecular Therapy · 2025-05-09 · 8 citations

  articleOpen access1st authorCorresponding
  PublisherOA PDFDOI

• CXCR3 Deficiency Alleviates Retinal Ganglion Cell Loss by Regulating Neuron–Astrocyte Communication in a Mouse Model of Glaucoma

  Investigative Ophthalmology & Visual Science · 2025-11-17 · 1 citations

  articleOpen access

  Purpose: Glaucoma is characterized by progressive retinal ganglion cell (RGC) death and optic nerve degeneration. Chemokines are a family of small, secreted proteins that mediate cell-cell communication, an essential process for maintaining microenvironmental homeostasis and regulating pathophysiological changes in multicellular organisms. However, the contribution of retina-derived chemokines to RGC loss in glaucoma remains poorly understood. Methods: We reanalyzed a publicly available retinal bulk RNA sequencing dataset from a mouse model of glaucoma to identify differentially expressed chemokines. A mouse model of microbead-induced glaucoma and primary RGCs and astrocytes were used to assess the role of the C-X-C motif chemokine ligand 10 (CXCL10)/C-X-C motif chemokine receptor 3 (CXCR3) axis in disease. Results: Several chemokines were significantly upregulated during disease progression, including CXCL10, previously implicated in neurodegeneration. In the microbead model, CXCL10 expression increased markedly by day 5 post-injection. At 6 weeks, deletion of CXCR3, the receptor for CXCL10, significantly prevented RGC loss and axonal degeneration without affecting intraocular pressure (IOP). Visual function, assessed by pattern electroretinography and visual acuity, was preserved in CXCR3-deficient mice. Mechanistically, CXCL10/CXCR3 signaling upregulated complement component 3 (C3) in astrocytes and C3a receptor (C3aR) in RGCs, driving toxic astrocyte-RGC crosstalk. Gene therapy using intravitreal injection of adeno-associated virus-mediated dominant-negative CXCL10 or pharmacological blockade of C3aR effectively reduced RGC loss. Conclusions: CXCL10/CXCR3 signaling is a key mediator of RGC loss in glaucoma. Targeting this pathway, along with its upregulated C3/C3aR axis, represents a promising IOP-independent therapeutic strategy for glaucoma.

  PublisherOA PDFDOI

• SPG302 protects retinal ganglion cells and preserves visual function by preserving synaptic activity in a mouse model of glaucoma

  Experimental Eye Research · 2025-09-16 · 1 citations

  articleOpen accessSenior authorCorresponding

  Glaucoma, a leading cause of irreversible vision loss worldwide, is an optic neuropathy characterized by optic nerve degeneration and retinal ganglion cell (RGC) death. Early glaucomatous damage is often associated with dendritic and synaptic abnormalities in RGCs, yet the mechanisms linking these synaptic alterations to RGC death remain unclear. In a mouse model of glaucoma, treatment with the clinical-stage, synaptogenic small molecule SPG302, a pegylated benzothiazole derivative, demonstrated neuroprotective effects, protecting RGCs and their axons in the glaucomatous retina and also improving retinal function as assessed by pattern electroretinogram testing. Elevated intraocular pressure disrupted synapses, as evidenced by reduced synaptophysin expression and homeostatic increases in Bassoon and PSD95 levels in the inner plexiform layer. SPG302 treatment effectively preserved synaptic integrity by reversing these changes. These findings highlight the therapeutic potential of SPG302 for protecting RGCs and preserving vision by modulating synaptic activity in glaucomatous neurodegeneration. • SPG302 protects retinal ganglion cells (RGCs) and their axons in the glaucomatous retina. • SPG302 preserves synaptic integrity in the glaucomatous retina. • SPG302 has therapeutic potential for protecting RGCs and preserving vision by modulating synaptic activity in glaucoma.

  PublisherDOI

• Inhibition of PFKFB3-Driven Glycolysis Downstream of Inflammarafts in Spinal Microglia Alleviates Chemotherapy-Induced Neuropathic Pain

  Journal of Pain · 2025-04-01

  article
  PublisherDOI

• Spg302 Protects Retinal Ganglion Cells and Preserves Visual Function by Preserving Synaptic Activity in a Mouse Model of Glaucoma

  SSRN Electronic Journal · 2025-01-01

  preprintOpen access1st authorCorresponding
  PublisherDOI

• AKAP1 regulates mitochondrial and synaptic homeostasis to enable neuroprotection and repair in retinal ganglion cell degeneration

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-11-27

  preprintOpen accessSenior authorCorresponding

  Glaucoma is a leading cause of irreversible blindness, characterized by progressive retinal ganglion cell (RGC) loss and optic nerve degeneration. Mitochondrial dysfunction plays a central role in this neurodegeneration, yet effective targeted therapies remain limited. Here, we identify the mitochondrial scaffold A-kinase anchoring protein 1 (AKAP1) as a critical regulator of RGC resilience and axon regeneration. AKAP1 expression is diminished in human glaucomatous retinas and experimental glaucoma models, correlating with elevated intraocular pressure, disrupted mitochondrial dynamics, oxidative stress, and synaptic instability. Restoration of AKAP1 via adeno-associated virus serotype 2-mediated gene therapy preserves RGC survival, promotes mitochondrial fusion and cristae integrity, enhances ATP production, and mitigates oxidative and apoptotic stress in mouse models of glaucoma and optic nerve injury. Transcriptomic profiling of AKAP1 knockout retinas reveals widespread dysregulation of mitochondrial and synaptic gene networks. Mechanistically, AKAP1 stabilizes synapses by promoting mitochondrial biogenesis, modulating calcium/calmodulin-dependent kinase II and synapsin phosphorylation, maintaining synaptophysin expression, and suppressing complement component C1q expression, thereby preventing early synaptic loss in glaucomatous neurodegeneration. Moreover, restoring AKAP1 expression facilitates axonal regeneration, preserves the central visual pathway, and maintains visual function. Collectively, these findings establish AKAP1 as a master regulator of mitochondrial and synaptic homeostasis and axonal regeneration and a promising therapeutic target for vision preservation in glaucomatous neurodegeneration.

  PublisherDOI

• IMPACT OF ALZHEIMER’S DISEASE ON SUPRACHIASMATIC NUCLEUS CONNECTIVITY, SLEEP REGULATION, AND CIRCADIAN RHYTHM

  Innovation in Aging · 2024-12-01

  articleOpen access

  Abstract Circadian disruption, notably sleep disturbances, serves as an early indicator of Alzheimer’s disease (AD), preceding cognitive symptoms such as memory impairment. Despite this, the underlying anatomical and functional mechanisms driving circadian disruption in AD remain elusive. The suprachiasmatic nucleus (SCN) serves as the central pacemaker regulating circadian rhythm and as the principal hub for entraining circadian rhythm. Here, we explore the relationships between SCN connectome evolution, sleep regulation, and circadian rhythm disruption in the APP/PS1 mouse model. In 3 to 8-month-old APP/PS1 mice, we obtained SCN image volumes via serial block-face scanning electron microscopy. We noted serval modifications in SCN connectomics, including a dendro-dendritic chemical synapse network reduction, crucial for synchronicity between SCN neurons, and a reduction of axonal boutons volume. In addition, we recorded electroencephalograms, electromyograms, temperature, and locomotor activity of 8-month-old WT and APP/PS1 mice to assess their sleep patterns. APP/PS1 mice displayed significantly reduced rapid-eye-movement sleep, associated with a reduced daily temperature amplitude and locomotor hyperactivity. Lastly, in 10 to 15-month-old APP/PS1 mice, we measure locomotor and metabolic activity change in response to acute light stimulation and light-dark cycle shift. APP/PS1 mice showed a decreased circadian fluctuation in metabolic activity and an impaired response to acute light pulse stimulation or phase shift. These preliminary results suggest considerable changes in the SCN connectivity may be responsible for circadian disruption in those with AD. Further investigation will evaluate the use of non-pharmacological approaches to mitigate the observed circadian disruption.

  PublisherOA PDFDOI

• AIBP: A New Safeguard against Glaucomatous Neuroinflammation

  Cells · 2024-01-21 · 15 citations

  reviewOpen accessSenior authorCorresponding

  Glaucoma is a group of ocular diseases that cause irreversible blindness. It is characterized by multifactorial degeneration of the optic nerve axons and retinal ganglion cells (RGCs), resulting in the loss of vision. Major components of glaucoma pathogenesis include glia-driven neuroinflammation and impairment of mitochondrial dynamics and bioenergetics, leading to retinal neurodegeneration. In this review article, we summarize current evidence for the emerging role of apolipoprotein A-I binding protein (AIBP) as an important anti-inflammatory and neuroprotective factor in the retina. Due to its association with toll-like receptor 4 (TLR4), extracellular AIBP selectively removes excess cholesterol from the plasma membrane of inflammatory and activated cells. This results in the reduced expression of TLR4-associated, cholesterol-rich lipid rafts and the inhibition of downstream inflammatory signaling. Intracellular AIBP is localized to mitochondria and modulates mitophagy through the ubiquitination of mitofusins 1 and 2. Importantly, elevated intraocular pressure induces AIBP deficiency in mouse models and in human glaucomatous retina. AIBP deficiency leads to the activation of TLR4 in Müller glia, triggering mitochondrial dysfunction in both RGCs and Müller glia, and compromising visual function in a mouse model. Conversely, restoring AIBP expression in the retina reduces neuroinflammation, prevents RGCs death, and protects visual function. These results provide new insight into the mechanism of AIBP function in the retina and suggest a therapeutic potential for restoring retinal AIBP expression in the treatment of glaucoma.

  PublisherOA PDFDOI

• AIBP Protects Müller Glial Cells Against Oxidative Stress-Induced Mitochondrial Dysfunction and Reduces Retinal Neuroinflammation

  Antioxidants · 2024-10-17 · 10 citations

  articleOpen accessSenior authorCorresponding

  Glaucoma, an optic neuropathy with the loss of retinal ganglion cells (RGCs), is a leading cause of irreversible vision loss. Oxidative stress and mitochondrial dysfunction have a significant role in triggering glia-driven neuroinflammation and subsequent glaucomatous RGC degeneration in the context of glaucoma. It has previously been shown that apolipoprotein A-I binding protein (APOA1BP or AIBP) has an anti-inflammatory function. Moreover, Apoa1bp−/− mice are characterized by retinal neuroinflammation and RGC loss. In this study, we found that AIBP deficiency exacerbated the oxidative stress-induced disruption of mitochondrial dynamics and function in the retina, leading to a further decline in visual function. Mechanistically, AIBP deficiency-induced oxidative stress triggered a reduction in glycogen synthase kinase 3β and dynamin-related protein 1 phosphorylation, optic atrophy type 1 and mitofusin 1 and 2 expression, and oxidative phosphorylation, as well as the activation of mitogen-activated protein kinase (MAPK) in Müller glia dysfunction, leading to cell death and inflammatory responses. In vivo, the administration of recombinant AIBP (rAIBP) effectively protected the structural and functional integrity of retinal mitochondria under oxidative stress conditions and prevented vision loss. In vitro, incubation with rAIBP safeguarded the structural integrity and bioenergetic performance of mitochondria and concurrently suppressed MAPK activation, apoptotic cell death, and inflammatory response in Müller glia. These findings support the possibility that AIBP promotes RGC survival and restores visual function in glaucomatous mice by ameliorating glia-driven mitochondrial dysfunction and neuroinflammation.

  PublisherOA PDFDOI

• Administration of Bicarbonate Protects Mitochondria, Rescues Retinal Ganglion Cells, and Ameliorates Visual Dysfunction Caused by Oxidative Stress

  Antioxidants · 2024-06-19 · 7 citations

  articleOpen accessSenior authorCorresponding

  Oxidative stress is a key factor causing mitochondrial dysfunction and retinal ganglion cell (RGC) death in glaucomatous neurodegeneration. The cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling pathway is involved in mitochondrial protection, promoting RGC survival. Soluble adenylyl cyclase (sAC) is a key regulator of the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling pathway, which is known to protect mitochondria and promote RGC survival. However, the precise molecular mechanisms connecting the sAC-mediated signaling pathway with mitochondrial protection in RGCs against oxidative stress are not well characterized. Here, we demonstrate that sAC plays a critical role in protecting RGC mitochondria from oxidative stress. Using mouse models of oxidative stress induced by ischemic injury and paraquat administration, we found that administration of bicarbonate, as an activator of sAC, protected RGCs, blocked AMP-activated protein kinase activation, inhibited glial activation, and improved visual function. Moreover, we found that this is the result of preserving mitochondrial dynamics (fusion and fission), promoting mitochondrial bioenergetics and biogenesis, and preventing metabolic stress and apoptotic cell death. Notably, the administration of bicarbonate ameliorated mitochondrial dysfunction in RGCs by enhancing mitochondrial biogenesis, preserving mitochondrial structure, and increasing ATP production in oxidatively stressed RGCs. These findings suggest that activating sAC enhances the mitochondrial structure and function in RGCs to counter oxidative stress, consequently promoting RGC protection. We propose that modulation of the sAC-mediated signaling pathway has therapeutic potential acting on RGC mitochondria for treating glaucoma and other retinal diseases.

  PublisherOA PDFDOI

Recent grants

• Mitochondrial Protection in Glaucomatous Optic Neuropathy

  NIH · $2.7M · 2020–2026

• Mitochondrial Dysfunction in Glaucomatous Optic Neuropathy

  NIH · $3.5M · 2009–2019

Frequent coauthors

• Keun‐Young Kim

  49 shared

• Robert N. Weinreb

  University of California, San Diego

  48 shared

• Guy Perkins

  University of California, San Diego

  21 shared

• James D. Lindsey

  University of California, San Diego

  20 shared

• Mark H. Ellisman

  University of California, San Diego

  19 shared

• Myung‐Hoon Chun

  15 shared

• Jonathan G. Crowston

  Royal Prince Alfred Hospital

  14 shared

• Dong‐Wook Lee

  Korea University

  13 shared

Labs

• The Ju LabPI

Education

• Ph.D., Ophthalmology

  University of California, San Diego

  2000

• M.S., Ophthalmology

  University of California, San Diego

  1996

• B.S., Biology

  University of California, San Diego

  1994