Honors & Awards
Knights Templar Eye Foundation Early Career Award, Knights Templar Eye Foundation (2023-Present)
Invited presentation, “Rising Stars.”, Western chapter of the Association of Biomolecular Resource Facilities (2021)
Retina Research Foundation/Joseph M, and Eula C. Lawrence grant, ARVO (2016)
Rio Mesa Fellowship, University of Utah (2012)
Doctor of Philosophy, University of Utah (2019)
Bachelor of Science, University of Utah (2013)
B.S., University of Utah, Biology (2013)
Ph.D., University of Utah, Neuroscience (2019)
Jeffrey Goldberg, Postdoctoral Faculty Sponsor
BDNF and cAMP are neuroprotective in a porcine model of traumatic optic neuropathy.
Traumatic optic neuropathy (TON) is a devastating condition that can occur after blunt or penetrating trauma to the head, leading to visual impairment or blindness. Despite these debilitating effects, no clinically available therapeutic targets neuroprotection or promotes axon regeneration in this or any optic neuropathy. Limited data in large animal models is a major obstacle to advancing treatments toward clinical therapeutics. To address this issue, we refined a surgical model of TON in Yucatan minipigs. First, we validated the model by demonstrating visual impairment by flash visual-evoked potential and retinal ganglion cell degeneration and death. Next, we developed and optimized a delivery method and non-toxic dosing of intravitreal brain-derived neurotrophic factor (BDNF) and cyclic adenosine monophosphate (cAMP). Finally, we showed that intravitreal injection of BDNF and cAMP rescued visual function and protected against retinal ganglion cell death and optic nerve axon degeneration. Together these data in a pre-clinical large animal model advance our understanding of and ability to model TON and further identify and develop candidate clinical therapeutics.
View details for DOI 10.1172/jci.insight.172935
View details for PubMedID 38194296
The Cousa objective: a long-working distance air objective for multiphoton imaging in vivo.
Multiphoton microscopy can resolve fluorescent structures and dynamics deep in scattering tissue and has transformed neural imaging, but applying this technique in vivo can be limited by the mechanical and optical constraints of conventional objectives. Short working distance objectives can collide with compact surgical windows or other instrumentation and preclude imaging. Here we present an ultra-long working distance (20 mm) air objective called the Cousa objective. It is optimized for performance across multiphoton imaging wavelengths, offers a more than 4 mm2 field of view with submicrometer lateral resolution and is compatible with commonly used multiphoton imaging systems. A novel mechanical design, wider than typical microscope objectives, enabled this combination of specifications. We share the full optical prescription, and report performance including in vivo two-photon and three-photon imaging in an array of species and preparations, including nonhuman primates. The Cousa objective can enable a range of experiments in neuroscience and beyond.
View details for DOI 10.1038/s41592-023-02098-1
View details for PubMedID 38129618
View details for PubMedCentralID 8211867
Retinal ganglion cell repopulation for vision restoration in optic neuropathy: a roadmap from the RReSTORe Consortium.
2023; 18 (1): 64
Retinal ganglion cell (RGC) death in glaucoma and other optic neuropathies results in irreversible vision loss due to the mammalian central nervous system's limited regenerative capacity. RGC repopulation is a promising therapeutic approach to reverse vision loss from optic neuropathies if the newly introduced neurons can reestablish functional retinal and thalamic circuits. In theory, RGCs might be repopulated through the transplantation of stem cell-derived neurons or via the induction of endogenous transdifferentiation. The RGC Repopulation, Stem Cell Transplantation, and Optic Nerve Regeneration (RReSTORe) Consortium was established to address the challenges associated with the therapeutic repair of the visual pathway in optic neuropathy. In 2022, the RReSTORe Consortium initiated ongoing international collaborative discussions to advance the RGC repopulation field and has identified five critical areas of focus: (1) RGC development and differentiation, (2) Transplantation methods and models, (3) RGC survival, maturation, and host interactions, (4) Inner retinal wiring, and (5) Eye-to-brain connectivity. Here, we discuss the most pertinent questions and challenges that exist on the path to clinical translation and suggest experimental directions to propel this work going forward. Using these five subtopic discussion groups (SDGs) as a framework, we suggest multidisciplinary approaches to restore the diseased visual pathway by leveraging groundbreaking insights from developmental neuroscience, stem cell biology, molecular biology, optical imaging, animal models of optic neuropathy, immunology & immunotolerance, neuropathology & neuroprotection, materials science & biomedical engineering, and regenerative neuroscience. While significant hurdles remain, the RReSTORe Consortium's efforts provide a comprehensive roadmap for advancing the RGC repopulation field and hold potential for transformative progress in restoring vision in patients suffering from optic neuropathies.
View details for DOI 10.1186/s13024-023-00655-y
View details for PubMedID 37735444
Campana cells in mammalian retinas
ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2023
View details for Web of Science ID 001053758304268
An uncommon neuronal class conveys visual signals from rods and cones to retinal ganglion cells.
Proceedings of the National Academy of Sciences of the United States of America
2021; 118 (44)
Neurons in the central nervous system (CNS) are distinguished by the neurotransmitter types they release, their synaptic connections, morphology, and genetic profiles. To fully understand how the CNS works, it is critical to identify all neuronal classes and reveal their synaptic connections. The retina has been extensively used to study neuronal development and circuit formation. Here, we describe a previously unidentified interneuron in mammalian retina. This interneuron shares some morphological, physiological, and molecular features with retinal bipolar cells, such as receiving input from photoreceptors and relaying visual signals to retinal ganglion cells. It also shares some features with amacrine cells (ACs), particularly Aii-ACs, such as their neurite morphology in the inner plexiform layer, the expression of some AC-specific markers, and possibly the release of the inhibitory neurotransmitter glycine. Thus, we unveil an uncommon interneuron, which may play an atypical role in vision.
View details for DOI 10.1073/pnas.2104884118
View details for PubMedID 34702737
The Susceptibility of Retinal Ganglion Cells to Optic Nerve Injury is Type Specific.
2020; 9 (3)
Retinal ganglion cell (RGC) death occurs in many eye diseases, such as glaucoma and traumatic optic neuropathy (TON). Increasing evidence suggests that the susceptibility of RGCs varies to different diseases in an RGC type-dependent manner. We previously showed that the susceptibility of several genetically identified RGC types to N-methyl-D-aspartate (NMDA) excitotoxicity differs significantly. In this study, we characterize the susceptibility of the same RGC types to optic nerve crush (ONC). We show that the susceptibility of these RGC types to ONC varies significantly, in which BD-RGCs are the most resistant RGC type while W3-RGCs are the most sensitive cells to ONC. We also show that the survival rates of BD-RGCs and J-RGCs after ONC are significantly higher than their survival rates after NMDA excitotoxicity. These results are consistent with the conclusion that the susceptibility of RGCs to ONC varies in an RGC type-dependent manner. Further, the susceptibilities of the same types of RGCs to ONC and NMDA excitotoxicity are significantly different. These are valuable insights for understanding of the selective susceptibility of RGCs to various pathological insults and the development of a strategy to protect RGCs from death in disease conditions.
View details for DOI 10.3390/cells9030677
View details for PubMedID 32164319
View details for PubMedCentralID PMC7140711
NMDA receptor activity regulates synaptic connections between retinal ganglion and bipolar cells
ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2018
View details for Web of Science ID 000442912505173
An unique subtype of BCs provides excitatory input to both ON and OFF synaptic pathways from both rods and cones in the retina
ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2018
View details for Web of Science ID 000442912509023
Virtual reality method to analyze visual recognition in mice.
2018; 13 (5): e0196563
Behavioral tests have been extensively used to measure the visual function of mice. To determine how precisely mice perceive certain visual cues, it is necessary to have a quantifiable measurement of their behavioral responses. Recently, virtual reality tests have been utilized for a variety of purposes, from analyzing hippocampal cell functionality to identifying visual acuity. Despite the widespread use of these tests, the training requirement for the recognition of a variety of different visual targets, and the performance of the behavioral tests has not been thoroughly characterized. We have developed a virtual reality behavior testing approach that can essay a variety of different aspects of visual perception, including color/luminance and motion detection. When tested for the ability to detect a color/luminance target or a moving target, mice were able to discern the designated target after 9 days of continuous training. However, the quality of their performance is significantly affected by the complexity of the visual target, and their ability to navigate on a spherical treadmill. Importantly, mice retained memory of their visual recognition for at least three weeks after the end of their behavioral training.
View details for DOI 10.1371/journal.pone.0196563
View details for PubMedID 29768429
View details for PubMedCentralID PMC5955493
Adult zebra finches rehearse highly variable song patterns during sleep.
2017; 5: e4052
Brain activity during sleep is fairly ubiquitous and the best studied possible function is a role in memory consolidation, including motor memory. One suggested mechanism of how neural activity effects these benefits is through reactivation of neurons in patterns resembling those of the preceding experience. The specific patterns of motor activation replayed during sleep are largely unknown for any system. Brain areas devoted to song production in the songbird brain exhibit spontaneous song-like activity during sleep, but single cell neural recordings did not permit detection of the specific song patterns. We have now discovered that this sleep activation can be detected in the muscles of the vocal organ, thus providing a unique window into song-related brain activity at night. We show that male zebra finches (Taeniopygia guttata) frequently exhibit spontaneous song-like activity during the night, but that the fictive song patterns are highly variable and uncoordinated compared to the highly stereotyped day-time song production. This substantial variability is not consistent with the idea that night-time activity replays day-time experiences for consolidation. Although the function of this frequent activation is unknown, it may represent a mechanism for exploring motor space or serve to generate internal error signals that help maintain the high stereotypy of day-time song. In any case, the described activity supports the emerging insight that brain activity during sleep may serve a variety of functions.
View details for DOI 10.7717/peerj.4052
View details for PubMedID 29158983
View details for PubMedCentralID PMC5694654
Retinal ganglion cell subtype specific circuits in retina
ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2016
View details for Web of Science ID 000394210603383
From the retina to the brain: retinal ganglion cell subtype specific visual circuits
ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2016
View details for Web of Science ID 000394210201132