NEI - National Eye Institute Grants

NEI - National Eye Institute

PROJECT SUMMARY / ABSTRACT Ocular disease may arise anywhere in the human retina, which spans roughly 70% of the eye's internal surface. While optical coherence tomography (OCT) has become the premier technology for retinal disease diagnosis, current instruments are incapable of accessing the peripheral retina due to slow imaging speeds. This proposal seeks to enable next-generation OCT technology that will make diagnostic screening and visualization of both the central and peripheral retinal areas a reality; increasing imaging speed roughly 50-fold will allow wide-field retinal imaging without increasing procedure time. This advancement is empowered by a novel laser technology, stretched-pulse-mode-locking, recently developed for OCT by the founders of Bluebird Photonics. This Phase I STTR support will allow Bluebird to refine the SPML laser design and advance from a prototype to a turn-key, environmentally robust commercial laser. Specific aims include the implementation of a bias-free, Sagnac-loop amplitude modulator and the development of a closed-loop locking mechanism to ensure a stable synchronization between the modulator and the optical cavity resonance. The resulting laser will offer a significant advance over existing commercial OCT technology in speed (5 MHz vs ~100 kHz), cost, stability, reliability, and ease of integration. Commercial SPML lasers will serve as a catalyst for further development of ultrawide-field OCT instrumentation and support clinical evaluation across a range of diseases.

NEI - National Eye Institute

Project Summary/Abstract Myopia is the most common eye condition worldwide, where distant objects appear blurry. Typically, myopia develops during childhood/adolescence but increases the risk of developing vision-threatening conditions, including macular degeneration, retinal detachment, and glaucoma later in life. Furthermore, uncorrected distance refractive error has been estimated to result in a global loss of productivity of $202 billion annually. The rapid increase in myopia prevalence also known as the “Myopia Boom” is alarming, but existing treatments are only partially effective or induce significant adverse effects. We have discovered that indigo light can completely suppress a strong myopiagenic stimulus in a near-primate model. Based on extensive preclinical research, we have identified the most effective indigo wavelengths for the suppression of myopia. Importantly, our discovery is consistent with the environmental origin of the Myopia Boom, where sunlight, with its abundant indigo photons, is protective and time spent indoors, where indigo photons are mostly absent, is a risk factor. Based on this discovery, we propose a new modality for the treatment of myopia progression in children and adolescents: indigo light emitting eyewear. This is an exciting treatment strategy because it may enable a highly effective, safe, noninvasive, simple to use, and cost-effective treatment for childhood myopia. In this Phase I project, we propose (i) to advance technical merit by developing a new prototype for low volume production and formal safety evaluation; and (ii) to evaluate feasibility by performing a pilot clinical study in young adults assessing tolerability, usability and safety. If successful, we will have established technical merit and feasibility for a fully powered clinical trial to assess efficacy in myopic children.

NEI - National Eye Institute

This proposal seeks support for students and junior investigators (travel awardees) to attend the 2025 International Society for Eye Research (ISER)/BrightFocus Foundation (BFF) glaucoma meeting titled "Concepts and Breakthroughs in Glaucoma" to be held October 8th-11th, 2025 at the Emory Conference Center and Hotel in in Atlanta, Georgia. As in past meetings, our goal is to bring together basic scientists, clinician-scientists, students and fellows for presentations and in-depth discussions on recent exciting research advances and developments in the molecular mechanisms underlying glaucomatous pathology, both in the conventional outflow tract and the optic nerve head. We have already recruited three thought leaders in glaucoma to deliver keynote lectures. As in past meetings, platform sessions will be selected exclusively from submitted abstracts, with one session reserved for travel awardees. We are also organizing again a one-day "crash course" in glaucoma for people newcomers to the field and students/junior investigators, consistent with our goal of increasing young scientist participation. The Specific Aims of the conference are to: 1. Enhance the emerging careers of at least 30 young investigators working in glaucoma research by providing travel awards. 2. Provide a forum for the dissemination of the most recent advances in glaucoma research. 3. Create an environment that facilitates the exchange of novel ideas among basic and clinician-scientists, fostering opportunities for collaboration among vision scientists with multiple scientific expertise. 4. Bring together scientists working in disparate areas of glaucoma research. We anticipate that this meeting will provide state-of-the-art information on recent advances in glaucoma and serve as an important resource for those involved in the translation of these findings into novel therapeutics. The conference will also provide new opportunities, avenues for new discovery, and a forum to develop potential collaborations among the attendees. The requested funds will support the travel, accommodation and registration of at least 30 trainees to attend this focused meeting.

NEI - National Eye Institute

PROJECT SUMMARY Global Ophthalmology is an expanding field within ophthalmology that unifies the local and international community to advance research, clinical care, education, and policy to prevent blindness worldwide. The Global Ophthalmology Summit is the only United States (U.S.) based meeting that delivers in depth and focused content in research in global eye health and health equity. It brings together leaders to create community and foster collaboration amongst meeting participants which is an opportunity to captivate a young audience to lay the foundation for future collaborations, mentorship, and inspire a career in vision science. Key research topics addressed include global scale collaborative research consortia, disease-specific interventions, technology and innovation, sustainability, education, and advancing eye health systems in the U.S. and globally. The resources sought in this proposal aim to enhance the participation of young researchers within the field of global ophthalmology through the following aims. In aim 1 we want to provide an opportunity to strengthen the global eye research community by bringing local and international expertise together to focus on innovative solutions to prevent and treat blindness worldwide. In aim 2 our goal is to create collaboration through providing intentional meeting content amongst the diverse group of attendees. In aim 3 we want to support innovative vision research in global ophthalmology of trainees and early career investigators. The mission of the Global Ophthalmology Summit is in alignment with the National Eye Institute’s new strategic plan to drive innovative vision research, foster collaboration, build global research consortia, inspire and recruit a diverse workforce, and educate our community and policymakers on the pressing needs of vision research. The National Eye Institute’s cross cutting areas of research emphasis addressed in past and future Summits include genetic research, data science, individual quality of life, and public health and disparities research.

NEI - National Eye Institute

Dry Eye Disease (DED) affects 20% of the global adult population, with higher rates in developed countries like the USA. It significantly impacts quality of life, productivity, increases healthcare costs, and can lead to vision loss if untreated. Current therapies are incapable of addressing chronic DED as they cannot be used long-term due to their toxicity. Our innovative First-In-Class mitochondrial technology targets the root cause of DED by addressing oxidative stress and mitochondrial dysfunction, which induces Meibomian Gland Dysfunction (MGD), a predominant cause of DED. Due to its unique mechanism of action, our drug candidate is safe for long-term use and offers a broader therapeutic window. This noninvasive treatment promises to revolutionize eye care and provide a sustainable solution to this widespread health challenge. Our proprietary small molecule lead candidate exhibits dose dependent free radical scavenging potential with calculated IC50 of 2.1µM and was found to protect various ocular cell lines against oxidative stress. It was found to be highly efficacious in reducing Benzalkonium chloride induced dry eye, tissue damage and vascularization in mice model of dry eye. An ophthalmic safety study suggests that an acute TID dose of our candidate as eye drops up to 30 µg/eye (total dose of 90 µg/eye/day) was well tolerated in New Zealand White rabbits. We have secured our invention by the filing of patent applications in the USA (US2021163159081), China (CN2280008594), India (IN202317001652), Canada (CA3205099A1), EU (EP22767950.3), Brazil (BR 1120230181097), Australia (AUS 2022234307) and Japan (JP2023-555226) for compounds, compositions, and their method of use. The novelty of our invention is confirmed by a written opinion from USPTO and an enhanced freedom to operate searches by qualified patent attorneys. DED is a multifactorial indication; therefore, in proposed SBIR phase I, our proposed studies entail In vivo characterization of lead candidates in desiccating stress/scopolamine (DSS) model of DED in mice working through varied etiologies. We also propose to evaluate the toxicity of our lead in repeated dose 7-day rabbit model of toxicity with PK parameters and local biodistribution in eye tissues of rabbits. Successful completion of proposed studies will be followed by submission of a phase-II SBIR to conduct a set of IND-enabling pre-clinical studies, manufacturing process scaleup and development, and analytical method validation, GLP toxicity studies with recovery group. Setup of in-house eCTD software interface and electronic submission gateway (ESG) with FDA and relevant certifications of personnel and workstation infrastructure will also be included in the SBIR phase-II application. We have assembled an experienced team consisting of chemists, drug discovery and bench to bedside drug product development experts, pharmacologists, ocular pharmacokinetics, toxicologists, ophthalmologists, regulatory experts, and industry partners. We are confident of successfully completing the proposed work.

NEI - National Eye Institute

Project Summary Cephalopod neuroscience offers a unique perspective in comparative brain research. Similar to vertebrates, cephalopods have evolved large, complex brains, enabling remarkable sensory, motor, and cognitive abilities. They exhibit sophisticated behaviors such as independent control of eight flexible arms, dynamic skin patterning for camouflage, and advanced learning and decision-making capabilities. Understanding the cephalopod nervous system has the potential to uncover fundamental principles of brain organization and function across species. Despite their fascinating neurobiology, the mechanistic workings of cephalopod brains remain largely unexplored. However, recent technological advances have catalyzed rapid progress and an influx of new researchers into the field, leading to the establishment of the first Cephalopod Neuroscience Gordon Research Conference. This meeting will bring together scientists from diverse areas of cephalopod research, including genomics, neural development, systems neuroscience, computation, and tool development. Our key objectives are to: (1) foster knowledge exchange and highlight recent discoveries, (2) cultivate an engaged and collaborative research community, and (3) facilitate resource and technique sharing. A strong emphasis will be placed on supporting trainees to ensure broad participation, and provide a strong foundation for this new Gordon Conference in the future. By combining cutting-edge science with community-building efforts, this conference aims to accelerate advances in cephalopod neuroscience and provide insight into broad principles of brain function.

NEI - National Eye Institute

Project Summary The 2026 Gordon Research Conference (GRC) on Photosensory Receptors and Signal Transduction (PRST) will be held in Ventura CA. The conference incorporates leading experts on diverse photosensory systems allowing for a comprehensive understanding of how nature employs cofactor chemistry to allow organisms to sense and adapt to their lighting environment. A comprehensive understanding of photoreception and signal transduction has a wide impact on human health and disease. For instance, for vertebrate vision subtle defects within the phototransduction pathway impacts retinal development and retinal degeneration, leading to conditions such as photophobia, visual acuity, night-blindness, loss of vision, as well as numerous other disorders of vision. Notably, defects in non-visual photo responsive systems within the eye have also been implicated in mood and sleep disorders, circadian dysfunction, and pupillary responses. To address these issues, it is essential to dissect and delineate how subtle alteration in cofactor identity, protein structure, and signaling pathways impacts defects in signaling and/or facilitates evolutionary adaptation to unique lighting environments. As a result, the format of the conference is unique in three essential elements: 1) Invited speakers will cover the entire range of physical, chemical, and biological factors gating light-responsive signal transduction in organisms. The comprehensive focus beginning from initial photon absorption, changes in cofactor chemistry, and structural transitions in photoreceptor proteins, to changes in organism physiology and ecological impacts affords unprecedented insight into how organisms harness photon absorption to mediate physiological responses. 2) Invited speakers cover the entire range of natural photoreceptors, providing deep understanding of how nature tunes small molecule cofactors, protein structure, and signaling pathways to allow for exquisite sensitivity to a wide range of wavelengths and light intensities. 3) These elements allow for an additional focus on applied practical applications to harness or manipulate photoreceptor function through optogenetic tools, or interventional treatments. The program structure and invited speakers for the GRC and associated Gordon Research Seminar (GRS) are designed to maximize interaction between established investigators, new investigators, and trainees from diverse disciplines to foster an exchange of ideas and scientific viewpoints to catalyze new interdisciplinary approaches to delineate photosensory responses and to engineer new technologies. The GRS provides an opportunity for junior scientists to meet and present their work in an environment of peers prior to the GRC. The GRS incorporates social, scientific, and mentoring to develop a sense of belonging, community, and inclusivity. Mentoring sessions have been chosen to encompass both academic and industrial career pathways to facilitate career growth and networking opportunities. The thoughtfully coordinated PRST GRC/GRS will position researchers to address the field’s most critical scientific challenges, while also motivating trainees to leverage their expertise in pursuit of emerging frontiers in photochemistry and photobiology.

NEI - National Eye Institute

Abstract Age-related macular degeneration (AMD) and related macular dystrophies (MDs) are leading causes of adult blindness with limited treatment options. AMD/MDs can present in two forms, geographic atrophy/GA (dry form) and choroidal neovascularization/CNV (wet form). There is strong evidence linking sterile inflammation to AMD/MD pathogenesis and two complement pathway inhibitors are already approved by FDA for treating GA in the dry form of AMD. However, due to limited therapeutic impact and adverse effects of complement inhibitors and other approved drugs for both dry AMD and wet AMD, there is a significant need for novel therapies for AMD/MDs. Our recently published data and preliminary studies identified secretory phospholipase A2-IIA (sPLA2-IIA), a pro-inflammatory enzyme, as a key molecular player in AMD/MD pathogenesis. AMD/MD primarily affect the retinal pigment epithelium (RPE) cells in the eye and patient-derived induced pluripotent stem cell- RPE (iRPE) from AMD and 2 distinct MDs showed elevated levels of sPLA2-IIA. Furthermore, AMD/MD iRPE cultures and AMD donor eyes showed elevated sPLA2-IIA levels in drusen, a pathological hallmark of early AMD/MD that is the key driver of later stage pathologies in AMD/MDs. Notably, pharmacological modulation of sPLA2-IIA activity in AMD and MD iRPE cultures led to reduced drusen. In addition, directly linking elevated sPLA2-IIA activity to AMD/MD pathology, sPLA2-IIA overexpression led to AMD-associated pathological alterations (drusen, Bruch’s membrane thickening, RPE thinning, CNV and visual deficits) in C57BL/6J mice. Altogether, these studies provide a strong rationale for targeting sPLA2-IIA activity in AMD/MDs. Toward this goal, we propose to develop proteolysis-targeting chimeras (PROTAC) compounds for specific inhibition of sPLA2-IIA in AMD/MDs. In initial experiments, we have synthesized a ‘lead‘ PROTAC (UR-00059) that can induce degradation of sPLA2-IIA in iRPE cells with half-maximal degradation concentration DC50 of 295.5 nM. The following milestone-driven aims will allow us to develop an effective PROTAC-based therapy targeting sPLA2-IIA for AMD/MDs. Aim 1: Optimize UR-00059 structure and activity and characterize the target engagement in vivo; Aim 2: Conduct in vivo efficacy studies and non-GLP absorption, distribution, metabolism, and toxicology of UR-00059; Aim 3: Perform IND enabling studies and obtain FDA approval for human testing. Ultimately, the proposed studies will develop a novel PROTAC-based therapy for targeting inflammation, drusen and consequently late stage pathologies of AMD and related MDs.

NEI - National Eye Institute

Project Summary: BB4B – BuddyBooks for Braille Significance: Braille literacy is critical for braille learners and readers (BLR) students’ educational success, employment opportunities, and independence. However, BLRs (grades 4-12) face two key challenges: (1) they need more practice reading outside of limited sessions with their specialized Teachers of Students with Visual Impairments (TSVIs), and (2) they receive insufficient instructional time due to a national shortage of over 5,000 TSVIs. This lack of consistent, independent practice significantly impacts literacy development, leading to lower academic outcomes. Innovation: BuddyBooks for Braille (BB4B) is an AI-powered braille literacy system that extends the successful BuddyBooks model to BLRs. It enables AI-assisted co-reading by integrating refreshable braille displays with Speech Recognition to analyze BLR oral reading and provide targeted feedback, it supports independent literacy practice with structured, interactive braille reading outside of TSVI sessions, it provides access to over 1 million books, ensuring BLRs have engaging, high-interest content to build fluency and comprehension, and it empowers TSVIs with an accessible Teacher Dashboard to monitor BLR progress and tailor instruction based on AI-driven reading insights. Research Questions: Phase I project assesses the feasibility and effectiveness of BB4B for improving braille literacy. The questions are: (1) To what extent does BB4B improve reading fluency, word recognition, and comprehension for BLRs? (2) How engaging and usable do TSVIs and BLRs find BB4B for braille reading practice? Prior Work: BB4B builds on the success of two prior research projects: (1) BuddyBooks, an NSF-funded AI-assisted reading platform used by thousands of struggling readers, which demonstrated a 24% fluency improvement in students with dyslexia and reading difficulties and (2) Braille AI Tutor, funded by Microsoft AI for Accessibility, which successfully used AI-driven speech recognition to support braille literacy development through interactive storytelling. BuddyBooks has met the criteria for the Dept. of Education’s ESSA Tier 3 and Tier 4 standards of efficacy. Specific Aims: Using an Expert Team of TSVIs and braille literacy education researchers to advise our Software Team, we will (1) define the specifications and create the BB4B prototype, integrating AI-powered speech recognition with refreshable braille displays to support independent co-reading, (2) conduct usability testing with TSVIs and BLRs to ensure accessibility, effectiveness, and ease of integration into literacy instruction while iteratively improving the prototype and the Training Guide and (3) evaluate feasibility and impact through a pilot study with 45 BLRs, using a standardized literacy assessment, measuring improvements in fluency, phonological awareness, and comprehension over 12 weeks.

NEI - National Eye Institute

PROJECT SUMMARY/ABSTRACT This proposal seeks to fund and support trainees and junior faculty to attend the “Emerging Innovators in Ophthalmology Workshop” which will occur July 2026 at Stanford University with plans to make this a regular annual offering. Continued innovation in treatment, diagnosis and prevention of ophthalmic disease is critical for improving patient outcomes and reducing gaps in population health. Increasingly we recognize that innovation requires specific training and mentorship which is not broadly available. A specialized approach to evaluating clinical problems and creatively identify solutions has become codified and widely recognized around the world as the “Biodesign” approach upon which both the Stanford Byers Center for Biodesign Fellowship and, subsequently, the Stanford Byers Family Ophthalmic Innovation Fellowship Program are based. The “Emerging Innovators in Ophthalmology Workshop” will be an all-day course convened on Stanford campus to provide the framework of this approach and resources which attendees can use to further engage in the Biodesign process. Recognizing the importance of mentorship, senior faculty who both teach and engage in innovation will be present throughout the course and small group workshops to develop connections with the attendees. Additionally, each attendee will be connected with a formal innovation mentor based on their interest at the conclusion of the workshop with the expectation of regular meetings in the following year. Our objectives for the course are: (1) to teach the core principles of the Biodesign approach with a focus on Ophthalmic Innovation to ophthalmology residents, post-doctoral scholars, and junior faculty in hopes for encouraging innovation and (2) to provide and develop long term mentorship for clinical and scientific trainees as well as junior faculty in support of ongoing innovative work.

NEI - National Eye Institute

PROJECT SUMMARY The 2026 Gordon Research Conference (GRC) and Gordon Research Seminar (GRS) on Visual System Development are a paired set of biennial meetings that bring together investigators studying development, disease, and evolution of the visual system. Over the years, these meetings have provided an exciting and unique forum in which to explore the similarities and differences underlying visual system development and function across a broad range of species. The goal of these meetings is to foster an appreciation of common principles that mediate the construction and function of the visual system in diverse organisms, and to share the latest exciting new ideas and findings on this topic. By including sessions that highlight emerging topics with translational impact, such as “Retinal Stem Cells, Repair, and Regeneration”, and “Developmental Disorders, Diseases, and Aging of the Visual System”, the meeting is also expanding its scope and stimulating crosstalk between developmental biologists and investigators focused on translational aspects of vision science. The GRS provides a unique platform for students and postdoctoral research fellows in the visual research field to share current, unpublished research amongst their peers and receive career mentorship in the vision science field. The format of the GRC and GRS meetings provides a highly interactive and stimulating venue for cross- fertilization of ideas and development of new collaborations. The Visual System Development GRC has established a reputation as the leading conference in its field, and it is the only meeting on the topic that brings together vision researchers working on the full range of experimental systems in the field, ranging from Drosophila to human. The current proposal requests funds to help defray conference fees for attendees at both meetings. The Visual System GRC and GRS will feature scientists at the cutting edge of the field, with careful attention taken to ensure involvement of researchers around the world, with participation from scientists at all stages of their careers.

NEI - National Eye Institute

ABSTRACT / SUMMARY Glaucoma is the leading cause of irreversible blindness, driven in most patients by elevated intraocular pressure (IOP) from increased resistance in the eye’s drainage tissue, the trabecular meshwork (TM). While IOP-lowering eye drops help, real-world adherence is poor, side effects are common, and benefits vanish when dosing lapses. This Phase I STTR develops a one-time, adherence-independent therapy: a lipid nanoparticle (LNP) encapsu- lating CRISPR/Cas9 mRNA and guides specific to ROCK1/2 delivered by an intracameral injection to the TM cells, relaxing the tissue, enhancing aqueous outflow, and thereby lowering IOP without daily medication. The approach is pathway-targeted (not mutation-specific) and is intended to benefit the broad primary open-angle glaucoma population. AIM 1 will optimize guide RNAs and LNP formulation for efficient, safe ROCK editing across high-, intermediate-, and low-flow TM regions (the latter being disproportionately expanded and stiff in glaucoma). Editing will be quantified by next-generation sequencing, and traction force, fibrotic marker, and tis- sue viability read outs will all be used to select a lead LNP-Cas9/gROCK candidate. AIM 2 will perform a head-to-head comparison in paired ex vivo perfused human glaucomatous eyes: one eye will receive a single LNP-Cas9/gROCK treatment and the fellow eye will receive daily Rhopressa (0.02% Netarsudil ophthalmic so- lution) dosing, a ROCK-inhibitor. We will measure outflow facility continuously, map segmental outflow before/af- ter treatment, and assess TM stiffness, cell-level contractility, on-target editing, and safety. Success is defined by >50% editing in the TM, <0.3% off-target editing, increases in outflow facility and IOP homeostasis, reductions in contractility and stiffness, with no safety concerns. The work is innovative in three ways: (i) nonviral LNP gene editing in anterior segment tissue; (ii) pathway-level editing to replicate a validated mechanism with durable effect; and (iii) spatially resolved linkage of molecular editing to functional and biomechanical outcomes in human donor eyes, the closest proxy to in vivo human physiology. An experienced, cross-disciplinary team in ocular gene delivery, outflow biology, biomechanics, and clinical translation will execute the plan using established cores and protocols. If successful, this project will justify IND-enabling studies in Phase II, advancing a first-in-class, one-time therapy that could transform glaucoma care by removing the adherence barrier while preserving vision.

NEI - National Eye Institute

Abstract Carolina Instruments is developing Pupil-Light, a wearable platform technology for acquiring high-speed, high- fidelity measurements of saccades, microsaccades, and pupil dynamics in real-time. Quantitative data on physiological signals such as saccades (rapid eye movements) and pupillometry (changes in pupil size) is critical for neuroscientists and physicians who aim to link these responses to behavioral or neuronal activity. Existing wearable eye-tracking systems suffer from low sampling rates and limited precision, making them inadequate for capturing rapid saccades and subtle pupil changes. These limitations hinder progress in neuroscience research and clinical diagnostic applications. Carolina Instruments’ Pupil Light addresses this gap by measuring pupil dynamics with unprecedented precision. Pupil Light’s simple camera-free design uses lightweight and low- cost materials to enable the field collection of previously unrecordable data. Our Pupil Light technology applies photoplethysmography techniques for the simultaneous measurement of numerous biometrics including fine eye movement and pupil size. By eliminating cameras, our system’s high sampling rate enables saccade- and microsaccade-tracking in real time without generating large volumes of video data. The compact and lightweight nature of the LED and sensor enables this noninvasive approach to seamlessly integrate into a convenient wearable form factor. The system’s ability to capture synchronized signals in real time streamlines data collection and improves experimental efficiency. Preliminary studies have demonstrated proof-of-concept acquisition of saccades and pupillary responses in a free-standing device; this project seeks to optimize these functions and validate their accuracy in a wearable prototype. Aim 1 will evaluate the accuracy and reliability of Pupil Light for detecting saccades and microsaccades under both head-fixed and wearable conditions. In head-fixed validation, participants will wear a photodiode-integrated printed circuit board (PCB) while their head is stabilized by a benchtop head fixation system, allowing for precise calibration and baseline measurement. In the wearable condition, subjects will have no chinstrap, instead relying on inertial measurement unit (IMU)-based motion compensation to correct for head movement. We will assess how well the wearable Pupil Light system stabilizes and corrects for motion artifacts compared to gold standard video-based eye tracking. Aim 2 will similarly employ both head-fixed and wearable configurations to assess the accuracy of Pupil Light for real-time pupil size tracking. The completion of this project will lay the foundation for Phase II efforts, including refining the device for use in human psychiatric studies and enhancements to real-time data reporting.

NEI - National Eye Institute

Project Summary Visual acuity (VA) is a key metric of retinal status in clinical trials and patient management, but measurements are often inaccurate due to the optical artifacts that are common in the aging eye. It is often unclear whether the retina, the optics, or both are the cause of reduced VA. The aging of the population has greatly increased visual impairment and blindness. The many treatment trials for age-related macular degeneration and diabetes make better VA measurements crucial. Critical barriers to accurate VA measurements remain with current wall charts or displays, whether computer screens or goggles. Pupil size is variable and usually decreased in older eyes, retinal illuminance is uncontrolled, and wavefront aberrations vary with pupil size and are uncontrolled. Wide field glare and crowding are problematic, especially for cataract patients with ghost images. Subjective refraction is typically prior to VA measurements. Traditional VA methods are problematic with an autorefractor, due to an unspecified or too large pupil and wavefront aberrations. The commonly used pinhole can reduce unwanted scattered light and defocus, but has decreased retinal illuminance and is sometimes difficult to position. Current VA methods lack quantification of variability. Two bottlenecks in patient flow are a) requiring subjective refraction instead of autorefraction b) measuring VA before pupil dilation. To address these, Aeon built a series of Potential Vision Tester (PVT) prototypes that project visual stimuli using Maxwellian view and a 3 mm pupil. Data to date indicate that PVT VAs are better than VAs from a wall chart or electronic display, when correcting sphere and cylinder. Correction of higher order aberrations thus far does not improve VA or SD. To demonstrate the feasibility of a more accurate VA test in the price range of electronic VA tests, in Aim 1 we will design, build, and optimize a new visual stimulation channel with tunable sphere and astigmatism correction. We will test 10 controls using the new tunable lenses, measuring wavefront aberrations for Zernike orders 1 – 6 for both the PVT and subject, then compare objective vs. subjective sphere settings and the resulting VAs. To reduce bottlenecks and inaccuracy in VA measurements due to anterior or posterior segment pathologies, in Aim 2 we will compare PVT VA vs. standard BCVA in selected groups (10 Ss/group). In Aim 2.1 we will compare VA measured with pupil dilation to > 5 mm vs. natural pupil using the PVT+pupil camera. In Aims 2.2 and 2.3, we will compare and model data for PVT VA vs. the BCVA with the DRCR/standard clinical protocol for patients with a) cataract, b) posterior capsule opacification post surgery, c) cylinder > 2.5D, d) coma > 0.4 microns for 3rd + 5th order Zernike polynomials, and probe combinations of measured higher order aberrations. An improved VA test device could lower barriers to new treatments and individual patient care, improve screening, or benefit AI models by leveraging robotic ophthalmic instruments with on board pupil alignment, as either a stand-alone or combination unit.

NEI - National Eye Institute

Program Summary/Abstract In vivo monitoring of ocular tissues is an essential component of modern vision science research. Common approaches in both the lab and clinic to examine the eye and retina include scanning laser ophthalmoscopy (SLO) and optical coherence tomography (OCT). Although there is a strong desire for multiple National Eye Institute (NEI)-funded researchers at Washington University to use live imaging techniques to study eye development and degeneration, we have limited capabilities do a lack of any SLO device and an outdated and low quality OCT system. Currently, in vivo imaging is limited to the 2-photon setup of Dr. Williams, which is heavily used and customized making it difficult to meet the demands of our research group through collaborative research. Funds are requested to purchase an UltraEye dual function SLO/OCT microscope with adaptive optics capabilities. The UltraEye will be housed in our department’s newly renovated Visual Function Testing Core facility in the Department of Ophthalmology and Visual Sciences. The core User Group for the new instrument includes 11 faculty members from 3 academic departments who are working with eye development, function and therapeutics development for degeneration. A total of 24 NEI-funded investigators along with the rest of the Washington University research community at large will have access to the SLO/OCT device. Additionally, since the high resolution OCT system is also capable of imaging superficial structures, we will make the system available for reservation via our already existing Facility Online Manager interface that is already established for our Histology, Molecular Biology and Microscopy Cores within the department. The new instrument will 1) Greatly expand in vivo imaging capacity within the Washington University vision research community for experiments with fluorescently labelled animals. 2) Vastly improve the quality of OCT imaging, while also providing high resolution SLO due to the adaptive optics features. 3) Provide new capabilities by powerfully combining SLO and OCT modalities for simultaneous volumetric structural scans. 4) Enable SLO/OCT imaging of non-traditional animal models not supported by current or most other commercial SLO/OCT microscopes. Members of the User Group are engaged in fundamental research into the causes and treatments of retinal ganglion cell degeneration, inherited retinal degeneration, choroidal neovascularization, macular degeneration, uveitis, cataract and corneal dystrophies. The requested instrument will contribute directly and substantively to progress in each of these clinically important areas.

NEI - National Eye Institute

Project Summary ICU care contributes to as much as 30% of total hospital costs and surgical complications occur in as many as 20% of operations, with a combined estimated annual cost to the U.S. of almost one trillion dollars. Devices that can reduce complications and lower these expenses are desperately needed. The pupillary light reflex is a cornerstone of both the neurological and ophthalmological examinations. This simple test provides the clinician with an enormous amount of objective information about the health of the brain and visual system, particularly in unconscious or sedated patients in the ICU after head trauma or cardiac arrest, who are at risk of sudden deterioration from brain swelling. Likewise, patients undergoing routine operations on the brain, heart, spine, and nasal sinuses are at risk of accidental loss of vision and there is no reliable method for assessing visual function in the operating room. The current standard of care in the ICU is to have the nurse manually open the eye and estimate the pupil’s response with a flashlight, which is subjective and unreliable, or use a quantitative, monocular, hand- held pupillometer once every few hours. Both methods are labor intensive, risk corneal injury, and only performed intermittently, which means that acute and dangerously high increases in brain pressure are often not identified in time. There is no reliable method for monitoring vision in the operating room, which can be accidentally lost during routine surgeries on the brain, spine, heart, nasal sinuses, and carotid arteries. Illumination Diagnostics is developing a continuous transpalpebral pupillometer to measure pupil responses through closed eyelids to solve these unmet needs. In this Phase 1 proposal, we plan to validate and optimize an adhesive eye patch design that uses infra-red light to continuously perform quantitative pupillometry, simultaneously through both closed eyelids with the following aims: 1) Use of computer modelling to design the device for maximal performance and safety, 2) Build a prototype transpalpebral pupillometer and develop image analysis software, and 3) Build an eye phantom to test and further optimize the prototype and train a machine learning algorithm. A successful device will enable clinicians to identify imminent brain or eye damage in their unconscious ICU or surgical patients and intervene earlier to preserve brain and eye function and save lives.

NEI - National Eye Institute

Project summary Two of the most common and debilitating eye-related diseases are age-related macular degeneration (AMD; ~20 million cases in the US) and glaucoma (~4 million cases in the US). The economic impact of these conditions is substantial and growing as our population continues to age, with an estimate of over $373 billion in annual lost productivity by 2050 in the US alone. Over the last 60 years multiple risk factors (RFs) for AMD and/or glaucoma have been discovered, with smoking, blood pressure, obesity, high cholesterol, cardiovascular disease, diabetes, poor diet, and sun exposure now considered ‘standard’ and, in some cases, modifiable. But even when combined with age, sex, race/ethnicity and genetics, the predictive ability of these RFs is still lower than desired. Novel biomarkers of risk that can better predict who is at high risk for AMD and/or glaucoma, and/or changes in optical coherence tomography angiography (OCTA) measures (e.g., retinal thickness; vessel density) may allow for earlier and more targeted intervention and are of high interest. There is considerable evidence that circulating fatty acids (FAs; esp. n3-FA - see the recent JAMA Ophthalmology paper by co-I Sala-Vila et al. on n-3s and diabetic retinopathy) can provide prognostic information regarding risk for eye health, independent of standard RFs. But, emerging data supports a role for other FAs as well. Data suggest that trans FA are potentially harmful, omega-6 levels are largely inconclusive, and saturated fats and mono-unsaturated fats (e.g., oleic acid, common in the mediterranean diet) have yielded widely disparate findings to date. As a clinical laboratory that has specialized in providing FA measurements, interpretation and customized behavioral interventions for the last 15 years, OmegaQuant Analytics (OQA) supports a large and growing customer base of researchers, clinicians, businesses, and individuals- including an increasing number of optometrists, ophthalmologists and other eye health experts. OQA is a leader in the at-home FA testing market through its innovative dried blood spot collection system, testing ~40,000 samples annually. In this project we will: Aim 1. Use machine learning to define RBC FA patterns that predict risk for 1) incident AMD 2) incident glaucoma or 3) related OCTA measures. We will begin by harmonizing eye health outcomes, fatty acids and covariate data from the FHS, WHIMS, MESA, and BPRHS yielding sample sizes of up to 19,922 total individuals with information on AMD or glaucoma outcomes over an average of 10+ years of follow-up. We will then apply statistical / machine learning algorithms to determine (Aim 1a) the extent to which we can separately predict changes in AMD and glaucoma from baseline RBC FA metrics. These analyses will lead to 2 unique sets of FA metrics that will predict risk for 1) incident AMD (the macular degeneration FA index, FAMADI), and 2) incident glaucoma (Glaucoma Fatty Acid Index, GAFI). Aim 2. Explore how FAMADI and GAFI can be leveraged to profitability. Proof of concept feasibility will set us up for larger-scale prospective studies and improved modelling in Phase II.

NEI - National Eye Institute

SUMMARY Rodents from the genus Acomys (Affrican Spiny mice) have recently emerged as a powerful model for regeneration, being capable of fully regenerating sections of skin without scarring including the development of new skin appendages. The regenerative capabilities of the Acomys species is not limited to the skin, with studies also demonstrating they can regenerate skeletal muscle tissue, cartilage, kidney, peripheral nerves and digits. Thus, the Acomys are a powerful animal model to understand the cellular and molecular mechanisms that promote regeneration with limited scarring in mammals. Aim 1a of this proposal will establish whether the Acomys cahirinus are capable of scarless corneal wound healing by comparing the regenerative capabilities of the cornea of A. cahirinus to the Mus musculus following alkali burn (AB). Aim 1b will then characterize and compare the mechanisms of wound healing between the A. cahirinus and M. musculus. This aim will establish for the first time whether A. cahirinus are capable of scarless corneal wound healing and identify the mechanism by which A. cahirinus are capable of regenerating a transparent cornea following AB. Our lab has been using the AB model on mice of diverse genetic backgrounds for well over a decade. Over the years, we have collated significant longitudinal data to show that when a group of wild-type mice on the same genetic background, such as C57BL/6J, are subjected to AB of equal severity, some mice are able to regenerate their corneas with limited to no scarring by day 14 (~18% of mice), while the others present corneal scarring (~82%). Curiously, our unpublished data show that the mice that present corneal scarring by day 14 present significant inflammatory cell infiltration and severe epithelial defect at day 1, while mice that are able to regenerate a transparent cornea by day 14 do not. Thus, excessive inflammatory infiltration within the first 24 hours following injury dictates whether the cornea will regenerate or suffer corneal scarring. Aim 2 of this proposal will characterize and compare the wound healing process between inbred C57BL/6J mice that are able to regenerate the cornea following AB to those that present corneal scarring, identifying for the first time key factors that direct corneal wound healing into wound resolution and regeneration instead of corneal scarring. Clinical Significance: Corneal scarring after trauma is a leading cause of vision loss in our society. To date, there are limited treatment options for preventing and treating corneal scarring, culminating in an urgent medical need for new therapeutics that can promote scarless wound healing. This proposal will identify key cellular and molecular mechanisms that regulate scarless wound healing establishing the groundwork for developing novel therapies for triggering scarless wound healing in the clinic.

NEI - National Eye Institute

PROJECT SUMMARY/ABSTRACT Fuchs endothelial corneal dystrophy (FECD) is a polygenic disease that affects 6.1 million Americans over 40 years of age. FECD is the leading indication for corneal transplant surgery in the U.S. Although the condition can be diagnosed early, it requires corneal surgery because no available therapy prevents disease progression. Unfortunately, the availability of donor corneal tissue is extremely limited (only 1 cornea is available for every 70 needed worldwide), and the risks of donor tissue failure (immediate risk) and graft rejection and failure (lifetime risks) are significant. In addition to preserving sight and circumventing the need for surgical intervention, medical therapy (e.g., eye drops) would avoid the following key issues: 1) high medical costs, 2) lack of available corneas, 3) lost productivity costs, and 4) long-term care costs associated with corneal transplantation. The need to develop an effective nonsurgical intervention is therefore urgent. In exciting preliminary studies, the S5G Therapeutics, Inc. research team—in tandem with experts at the University of Iowa—recently demonstrated that a cell surface iron (Fe) influx protein, transferrin receptor 1 (TFR1), is overexpressed in the corneal endothelial cells (CECs) of FECD patients. TFR1 overexpression in FECD is linked specifically to ferroptosis—a pathogenic mechanism of cell death characterized by lipid peroxidation and intracellular Fe accumulation. The overall goal of this SBIR Phase I project is therefore to develop, validate, and determine the feasibility of a targeted pharmacotherapeutic that is independent of specific gene mutations causing disease and that prevents the progression of clinical disease and need for surgery in FECD patients. Our screen of hundreds of anti-ferroptosis antioxidants indicated that the top performer was ubiquinol (the active and reduced form of coenzyme Q10). Our published data indicate strongly that ubiquinol prevents ferroptosis in FECD models. Thus, our central hypothesis is that therapies containing ubiquinol to target lipid peroxidation will greatly reduce cell death across a spectrum of FECD mutations and will prevent disease progression and the need for surgery. Ubiquinol is sensitive to heat and light with a very short half-life, and we have achieved a nanoparticle (NP)-based pharmacoengineering solution to render it practically useful. We intend to prove the feasibility of this novel approach via two Specific Aims: 1) Optimize the dosing of ubiquinol-loaded TFR1-targeted NPs versus controls, and 2) Determine the optimum time to initiate treatment with ubiquinol TFR1-targeted NPs versus controls. The approach is innovative, in that we will use a novel disease-dependent targeting strategy to develop mechanism-specific, first-in-class anti-ferroptosis antioxidant NPs to prevent FECD progression without surgery. The expected Phase I outcome is advancement of a novel eye drop to slow FECD progression and reduce the need for corneal transplant surgery, and will yield the best dosing frequency and initiation point for a Phase II validation/demonstration of topical use in a preclinical small-animal trial. Phase II success will be the basis for Phase IIB/Phase III studies focused on testing this treatment in human clinical trials and attaining ultimate commercial deployment.

NEI - National Eye Institute

Project Summary Inherited retinal diseases (IRDs) are a group of genetic blinding disorders that cause progressive vision loss, often resulting in blindness by early to mid-adulthood. In addition to economic burden, blindness and visual impairment have severe implications on quality of life for patients. The most common form of IRD, retinitis pigmentosa (RP), affects over 2 million people worldwide and approximately 100,000 in the US alone. With causative mutations identified in over 100 genes so far, the genetic heterogeneity underlying RP is a major barrier to treatment. No single gene accounts for more than 30% of the patient population, highlighting a massive unmet need for a gene-agnostic therapeutic that can treat many forms of RP. The goal of this Phase I STTR program is to develop AGN-001, a first-in-class, gene-agnostic, off-the- shelf retinal cell therapy to restore photoreceptor function in patients with IRDs. Agnos Therapeutics, Inc. (AgnosTx) was founded on the pioneering research from Mandeep Singh, MD, PhD and Robert Johnston, PhD of Johns Hopkins University, which showed that transplanted retinal cells restore photoreceptor function through cellular component transfer (CCT). CCT involves transfer of functional proteins from donor cells to diseased host photoreceptors through intercellular nanotubes, thus complementing a multitude of disease-causing mutations. AgnosTx’s CCT-based cell therapy, AGN-001, uniquely rescues existing patient photoreceptor function at earlier stages of disease, independent of gene mutation. This differentiates it from other retinal cell therapies or single- gene approaches, as it works without the need for synapse formation and cell integration. Previous studies in multiple mouse models of IRD have shown that transplanted wildtype photoreceptors can rescue retinal function through CCT. During this Phase I program, AgnosTx will collaborate with Drs. Johnston and Singh at Johns Hopkins to develop AGN-001 as a therapeutic suitable for preclinical evaluation and advance towards clinical studies. Aims include: 1) adapting the manufacturing process towards current Good Manufacturing Practices (cGMP) compliance; 2) generating and validating reporter lines to demonstrate the transfer of therapeutically relevant proteins by AGN-001; and 3) assessing subchronic toxicity and CCT efficiency of AGN-001 in vivo using a co-transplant strategy. Successful completion of these aims will provide the essential proof-of-concept and safety data to de-risk the program for investors and collaborators. This will enable future Phase II efforts focused on cGMP manufacturing scale-up and Good Laboratory Practices (GLP) toxicology studies to support an Investigational New Drug (IND). Our ultimate goal is to provide a broadly applicable treatment option for most patients with retinitis pigmentosa, a US market valued at over $14 billion, addressing a significant unmet need and patient burden.

NEI - National Eye Institute

Project Abstract This proposal aims to transform the accessibility of digital thematic maps for the 285 million blind and low vision (BLI) individuals worldwide. Thematic maps are essential for understanding complex data in various domains, including climate analysis, electoral processes, and emergency management. However, these maps are currently inaccessible to BLI individuals, as screen readers often fail to recognize them, and they lack customization options for low vision users. If an alternative is provided, it is a simple table lacking any geographic information. This project seeks to commercialize Audiom, an innovative, multimodal, and Large Language Model (LLM) chat-based digital map viewer. Unlike existing alternatives, Audiom is designed to be fully compliant with Web Content Accessibility Guidelines (WCAG), enabling BLI individuals to engage fully in scientific and civic domains. The project will develop Audiom from a prototype into a fully commercial platform that integrates with mainstream map tools, laying the groundwork for further research into non-visual and multimodal cartography. Audiom offers a unique visual experience for low vision users, allowing customization through speech, textures, and high contrast borders. For non-visual users, Audiom provides an auditory and tactile experience, enabling navigation through a map with arrow keys or touchscreen swipes, with pitch and speech indicating the value of features. The specific aims of this project are threefold: 1) Optimize user performance with the Audiom interface through user-centered design iterations; 2) Execute community-based comparative usability studies to evaluate Audiom's effectiveness for BLI and sighted users; and 3) Create, commercialize, and distribute a productionready Software Development Kit (SDK) for accessible digital thematic maps, facilitating easy integration with existing digital map tools. By achieving these aims, Audiom will not only make thematic maps accessible to BLI individuals, ensure compliance with the Americans with Disabilities Act (ADA) and the Rehabilitation Act for government entities, but also make mainstream the field of non-visual cartography. The commercialization of Audiom will empower BLI scientists, enhance civic participation, and improve the quality of life for BLI individuals by allowing them to use digital maps for the first time.

NEI - National Eye Institute

Project Summary/ Abstract Disturbances in the curvature of the human cornea can lead to visual defects like myopia, hyperopia, astigmatism, or keratoconus. Therefore, understanding how such curved refractive surfaces develop is crucial for preventing or treating these disorders. In this research proposal, I plan to use the Drosophila corneal lens as a model for the human cornea. The fly is an attractive model organism due to its plethora of genetic tools and quick life cycle; and additionally, it about 70% of genes are conserved between humans and flies. The corneal lens is a biconvex ECM structure that focuses light onto the photoreceptor rhabdomeres. A major component of the corneal lens is the polysaccharide chitin, and my preliminary findings suggest that alterations in chitin levels affect corneal lens shape. To explore this idea further, I will use fly genetics, super-resolution and electron microscopy to study the detailed role of chitin in corneal lens morphogenesis (Aim 1; K99). The retina contains a fixed number of non-neuronal central cells which secrete the various corneal lens components and also provide support to the corneal lens. My preliminary data show that an excess of either central or lattice cells affects corneal lens morphology. I will first analyze how varying the numbers of central and lattice cells changes corneal lens architecture, and then using transcriptomics I will identify the genes expressed in these cells during the pupal stage (Aim 2; K99/R00). Central cells also secrete the pseudocone beneath the corneal lens, which is analogous to the mammalian aqueous or vitreous humor. Our previous work identified three proteins in the pseudocone that influence corneal lens shape. Additional pseudocone components will be identified using TurboID to find binding partners of one of these proteins. These as well as transporters and ion channels will be tested for corneal lens shape defects and glaucoma-like phenotypes in flies (Aim 3; R00). This work will provide mechanistic insights into corneal lens morphogenesis, which may be relevant to human corneal development and diseases. To accomplish the proposed research, I will combine my existing skills in developmental genetics, biochemistry and cell biology with new skills learned during my K99 training, including super-resolution microscopy and transcriptomics. During my transition into an independent position, I will solicit advice from my mentors Drs. Jessica Treisman, Gira Bhabha, Holger Knaut, Erika Bach and Hyung Don Ryoo. Their scientific advice on fly genetics, quantitative imaging and transcriptomics along with their experience of grantsmanship, mentoring, lab management, publishing and establishing fruitful collaborations will prove invaluable. My long- term career goal is to head a research laboratory that will investigate the genetic, biophysical, cellular, and molecular regulation of corneal lens shape determination. Although I have made significant progress toward this goal with research experience and publications, I firmly believe that the additional technical and career training proposed during the K99 mentored phase is necessary for my successful transition to independence.

NEI - National Eye Institute

PROJECT SUMMARY Throughout childhood, individual neurons that make up our brain form connections, or circuits, between each other. These circuits guide the flow of activity across our brain for proper functioning. A fascinating feature of the brain is that it’s believed that both our genetics and our experiences as children can influence how neurons connect to each other. Understanding this process is critical to knowing how our childhood experiences influence brain development, and how disruptions in this process result in neurodevelopmental disabilities like Autism. Surprisingly, despite its importance, we have very little direct data on how these physical connections form during childhood development. Rather, our understanding of this process is largely based on interpretations of data that do not directly follow how neurons connect with each other. This is because until recently, these kinds of experiments were difficult if not impossible to do. However, our lab has developed technology that now allows us to investigate how circuits form in a clear and unambiguous way. With these new tools we will first ask how neurons make the correct connections during development by focusing on a well-studied circuit between the eyes and the brain. This circuit will allow us to ask how connections between the left and right eye properly form in concert together to ensure that what our eyes see gets correctly processed in the brain. In the second aim, we will ask how closing one eye, which will block activity, or visual “experiences” from that eye, disrupts this process. We believe that what we learn from studying this visual circuitry will provide clues to how neurons form circuits throughout the brain. We will conduct these experiments in the ferret because there is a lot of existing data on how this visual circuit develops in this animal that we can use to better interpret our results. Additionally, the ferret visual circuit and its brain more closely resembles the human brain relative to mice, another popular model organism in neuroscience. This will make it more likely that the lessons we learn in the ferret will also be true in humans. Overall, we believe results from our proposal will help better understand how brain connections form during childhood which may inform how much we need to worry about the environment our children grow up in. Our proposal might also help with treating neurodevelopmental disabilities by providing additional evidence for treating conditions early in life while the brain is forming new connections and is still amenable to therapies.

NEI - National Eye Institute

PROJECT SUMMARY Visual tasks, like reading print or recognizing faces, often require detailed spatial information collected under changing lighting conditions. In the retina, as light intensity varies so do the gain and kinetics of neural responses—a process called adaptation that prevents saturation and supports a consistent perception of contrast. A significant gap in knowledge is how light adaptation functions in the fovea—the central most region of retina responsible for high-acuity vision. Retinal circuit adaptation relies on signal pooling, and therefore adaptation may vary between foveal and peripheral regions that differ in convergence. Additionally, cone photoreceptors in peripheral primate retina are known to be asymmetric in their sensitivity to light increments vs decrements. Therefore, circuit adaptation may differ in ON and OFF visual pathways. The objective of this project is to use distinct primate retinal circuits—foveal vs peripheral and ON vs OFF—to determine how circuits with differing signal to noise ratios modulate gain and kinetics across light conditions. Aim 1 will determine the impact of convergence on properties of retinal circuit adaptation (gain, kinetics, noise, and time course) in the primate foveal vs peripheral midget and parasol pathways, as well as the contribution of synaptic inhibition as a potential mechanism for circuit adaptation to luminance. Aim 2 will determine how asymmetries inherited from cone photoreceptors shape the functional properties of adaptation in the primate ON vs OFF peripheral midget pathway. Given the importance of the fovea for our everyday vision, this work will bridge a gap in our knowledge of how foveal circuits adapt to changes in contrast over varying background luminance, critical for the function of high-acuity vision. These results will positively impact the pursuit towards prosthetic retinal implants that can recapitulate properties of foveal circuits by providing a template for function in diverse retinal circuits. The training plan described in this proposal is designed to enable me to develop the skills necessary to reach my career goal of an independent investigator. By following this plan with the guidance of my sponsor and co-sponsor, I will continue to learn new electrophysiology techniques to build a strong foundation in retinal circuit research. I will develop my writing, communication, teaching, mentoring, networking, and scientific outreach skills. This research will take place at the University of Wisconsin-Madison where the strong intellectual environment and availability of primate tissue from the Wisconsin National Primate Research Center will be leveraged.