Dr. Santa Tumminia
Acting Director, National Eye Institute
February 2020
UNIQUE PROPERTIES OF THE EYE DRIVE RESEARCH BREAKTHROUGHS
The vision community is excited to recognize the year 2020. As you know from your regular visits to the eye doctor, the goal is to maintain 20/20 vision. In 2020, the community is also anticipating the naming of a new NEI director. As NEI Director for nearly 20 years before leaving last July, Dr. Paul Sieving left a legacy that positioned NEI as a leader in neuroscience, regenerative medicine, genomics and gene therapy research, including his own gene replacement trial for an eye disease called retinoschisis.
Investments in vision research accelerate biomedical progress because eyes possess unique features. Eyes are accessible, enabling minimally invasive surgery and precise drug delivery. Eyes are relatively immune privileged, meaning many therapies can be administered without triggering an immune reaction. Furthermore, therapies can be administered in one eye, while the untreated eye serves as a baseline comparison to gauge the effect of the treatment—in science we call that the ideal internal control. For these reasons, the first FDA-approved gene therapy treats a form of childhood blindness caused by a mutation in a gene discovered at NEI. NEI is currently funding dozens of other promising gene-based therapies to treat eye disease. The field of gene therapy is once again being transformed, this time by a gene editing technology called CRISPR, which fixes specific misspellings in the patient’s own DNA. Editas Medicine, a biotech company building on work by NEI researchers is conducting the first-in-human CRISPR trial to help patients with vision loss caused by a mutation in CEP290, another crucial gene in the eye, which was also discovered by NEI scientists.
First-in-human clinical trials represent the cutting edge of science progress. NEI just received FDA approval to begin the first-ever trial using tissue derived from patient-derived human induced pluripotent stem cells (hIPSCs), reprogrammed adult cells that can be converted into other cell types. In dry age-related macular degeneration (AMD), light-sensitive retina cells die leading to vision loss. Researchers made iPSCS from AMD patients and grew them into retina patches to transplant back into the patient. NEI is also leveraging a major AMD clinical trial to create a valuable scientific resource: a repository of stem cell lines generated from consenting AMD trial participants. The lines can be turned into any human cell type enabling new avenues for basic discovery and drug development. These lines are especially valuable because the basic research can be mapped to patients’ deidentified clinical, imaging, and genomic data.
The NEI Audacious Goal Initiative (AGI) pioneers regenerative medicine in the retina to restore vision loss due to injury or degenerative disease. AGI has launched three key research consortia, to image individual cells in the eye as they respond to light, to identify factors that control cell regeneration in the visual system, and to develop animal models to test regenerative therapies. Furthermore, the NIH Regenerative Medicine Innovation Project, part of the 21st Century Cures Act, has funded 16 projects, one quarter of which are vision research. Finally, this fall, NEI will review submissions to the 3-D Retinal Organoid Challenge, a $1 million prize competition to develop functional mini-retinas in a dish for use in disease modeling, drug development and transplantation. In 2019, NEI created a new Office of Regenerative Medicine to catalyze collaboration and coordinate the extensive efforts in the field.
Artificial intelligence (AI) has revolutionized vision research and clinical care in recent years. NEI recently funded a clinical study that tested NGoggle, an easy-to-wear device that can assess vision loss by analyzing signals between the brain and eyes. This portable system based on AI and virtual reality can improve diagnostic testing for glaucoma, a leading cause of blindness in African Americans and Hispanics. The NEI Small Business program funds clinical studies developing AI and telemedicine imaging tools that can provide early detection and prompt diagnostics for glaucoma, diabetic retinopathy (DR), and retinopathy of prematurity (ROP), a significant cause of blindness for very low birthweight premature infants. Telemedicine provides new treatment options for rural and underserved communities. In January, FDA approved an algorithm developed by NEI researchers to diagnose ROP. In 2018, the FDA approved an AI diagnostic system, called IDx_DR partly built on NEI-supported research. IDx-DR analyzes retinal images to screen and detect DR, an important step in managing a disease that causes vision loss in over 30 million Americans.
NEW TARGETS AND NEW THERAPIES FOR IMPROVING EYESIGHT
Research advances in the past year have led to therapies to improve patient quality of the life and reduce vision loss. Dry eye can lead to pain and sensitivity to light, and disproportionately impacts post-menopausal women. Immune cells called neutrophils release a web-like material on the surface of the eye to trap bacteria outside of cells. However, in dry eye, this webbing can sometime induce an autoimmune reaction. An NEI clinical trial in dry eye patients demonstrated antibody eyedrops not only reduced biomarkers of inflammation but reduced corneal damage. Patients with elevated fluid pressure in their eyes are at risk for glaucoma; pressure creates mechanical strain on the sensitive nerve fibers exiting the eye, leading to neuron death and thus vision loss. Current treatments for glaucoma seek to increase fluid drainage to reduce eye pressure. New research demonstrated eye pressure and brain pressure are integrally connected. In animal models, altering brain pressure impacted fluid drainage in the eye.
The NEI Workgroup on AMD Pathobiology explores the disease from genes, to cells, to patients. While AMD genomics studies have revealed candidate disease-causing genes, a recent study used new single-cell sequencing to create a comprehensive human retinal atlas, and then used data analytics to identify culpable cell types. In addition to the retinal neurons, which are known to die in AMD, the analysis pointed to glia (neuron support cells) and blood vessels cells, providing potential new cell targets for therapy. As cells age, they eventually become senescent, losing their ability to divide and renew. Aged tissue that has accumulated senescent cells can attract inflammatory immune cells, which can lead to death of neurons. NEI researchers discovered that messengers derived from omega-3 fatty acids can target senescence genes in animal models of AMD and Alzheimer’s Disease, restoring tissue structure and promoting repair and regeneration, pointing the way to new therapies for both diseases. Treatments for the wet form of AMD, as well as DR, target VEGF, a growth factor that promotes sprouting of abnormal blood vessels in the retina. VEGF therapies have slowed or even reversed vision loss in many patients, but for others, new drug targets may be needed. A new study in a model of DR identified Angptl4, a different signaling protein that also stimulates vessel growth. Dicer is an enzyme that cuts apart RNA messages to silence gene expression. Recent research has also demonstrated its role in controlling inflammation in dry AMD disease pathways. However, a recent study showed that absence of this enzyme led to both dry and wet forms of AMD, an unexpected link between the two forms. The team rescued mouse models of AMD by treating with an existing gene therapy to replace the missing enzyme, providing promise for a leading cause of blindness.
2020 VISION FOR THE FUTURE
This year, NEI launched our More Than Meets the Eye 2020 campaign to focus on healthy vision. We have increased outreach to patients and providers through our 65 partner organizations. One popular tool is a virtual reality app that allows users to visually experience the impacts of various visual impairment. In March, HHS released the 2030 evidenced-based preventive health objectives for the Healthy People Initiative. The Vision Topic, led by NEI, includes new objectives to understand the impacts of screen time on eye development, to increase surveillance of eye health at the state level, and to increase access to comprehensive vision services in community health centers.
Finally, NEI is engaging the community in strategic planning. The Anterior Segment Initiative (ASI) focuses on the ocular surface, where the eye interacts with the outside environment. In October, we solicited input to identify key research questions for ASI. Last fall, we launched the 2020 Vision for the Future strategic plan, under the auspices of our Advisory Council. We reached out to researchers, patients, providers, and other vision stakeholders through a Request for Information receiving 252 responses. One theme that emerged was to address unmet needs in Cortical Visual Impairment (CVI), a leading cause of pediatric blindness, often caused by stroke or trauma in utero affecting brain development. NEI is enlisting expertise to help identify and diagnose CVI, and to develop effective visual rehabilitation tailored to CVI. Unlike past plans which have been organized around our six core anatomical programs, this plan will be organized around seven cross-cutting areas of scientific emphasis: 1) Genes to Disease Mechanisms 2) Biology and Neuroscience of Vision 3) Immune System and Eye Health 4) Regenerative Medicine 5) Data Science 6) Individual Quality of Life, and 7) Public Health and Disparities Research. We have recruited panels of vision scientists, clinicians, patients, and experts from other fields to critically review scientific progress, needs, and opportunities to ensure the best vision for 2020 and beyond.
Santa Tumminia, Ph.D.
Acting Director, National Eye Institute
Santa Tumminia has served as Acting Director, NEI since July 2019. She was selected as the NEI Deputy Director in November 2018, where she provides executive leadership and scientific expertise on NEI policies and initiatives, strategic and organizational leadership, research oversight and priority setting, and financial management. She has expertise in a wide range of vision research issues and has provided leadership on NIH-wide programs in genetics and genomic medicine, behavioral science, angiogenesis, nanomedicine, translational science and rare diseases. In 2019, she also temporarily assumed the role of Acting NEI Scientific Director, managing the NEI Intramural Research Program.
Dr. Tumminia earned her Ph.D. in Biology from Rensselaer Polytechnic Institute in 1987. In her postdoctoral training, she examined the protein-nucleic acid interactions involved in ribosome assembly at the Roche Institute of Molecular Biology, Department of Biochemistry, Hoffman La-Roche, Inc. She then joined the NEI Laboratory of Mechanisms of Ocular Diseases, where she studied the mechanisms of cataract formation and tested the efficacy of anti-cataract agents as well as HIV-1 protease inhibitors. She also designed a mechanical stretch device to model the effects of glaucoma. She then transitioned to the Foundation Fighting Blindness, where she ultimately became Director of Grants and Awards overseeing the Foundation’s entire research portfolio. In 2003, Dr. Tumminia was recruited back to NEI by NEI Director Paul Sieving, serving in various leadership capacities.
Key NEI accomplishments include designing and implementing the National Ophthalmic Disease Genotyping and Phenotyping Network or eyeGENE®, launched in 2006. This genomic medicine initiative for rare inherited eye disease is a public private partnership that bridges advances in ophthalmic disease gene identification to clinical care management and facilitates research and treatment efforts. Under her leadership, NEI developed international partnerships with scientists, eye health care providers, private industry, and 6,500 patients and family members. Dr. Tumminia has provided NEI leadership on stem cell policies and initiatives, recently building an NEI Office of Regenerative Medicine to catalyze collaboration. She was instrumental in the development and implementation of the NEI Audacious Goals Initiative in Regenerative Medicine. Other key initiatives include the Age-Related Macular Degeneration Integrative Biology Initiative, the Anterior Segment Initiative and establishing new offices in data science and population health.
Dr. Tumminia has received numerous awards including multiple NIH Director’s Awards for the NIH-wide Strategic Plan Working Group, and for leading the eyeGENE® Initiative. In 2018, she received the NIH Director’s Award in Mentoring. Her efforts led to increasing the number of female tenure-track investigators in the NEI intramural program, and she has also supported workplace diversity through the NEI’s Diversity in Vision Research and Ophthalmology (DIVRO) training program.