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The IRRF 2017-2018 BIENNIAL REPORT Sandra Blackwood, Editor Photos: Sandra Blackwood David Epstein Design: Robert T. Weathers BECOME A BENEFACTOR How You Can Help… 2017-2018 Today’s scientists play a crucial role in the universal struggle against debilitating eye diseases, but financial funding is needed to facilitate and sustain their efforts. Since 1998, the IRRF has granted nearly $23 million in support of scientific investigations targeting all structures of the human eye, with emphasis on finding the causes, prevention and cure of degenerative diseases. If you would IRRF BIENNIAL REPORT like to help with this challenge, please send your tax deductible contribution to: The International Retinal Research Foundation, Inc. Attn.: Sandra Blackwood, MPA, Executive Director 1720 University Boulevard Birmingham, AL 35233 www.irrf.org The IRRF Board of Directors

MICHAEL A. CALLAHAN, MD, JOHN S. PARKER, MD, has served as President since 2004 and gives generously serves as Vice President while devoting himself to private of his time. Since 1998, Dr. Callahan has held a faculty ophthalmology practice and teaching responsibilities in position as Professor of Ophthalmology in the Department of the UAB Department of Ophthalmology where he trains Ophthalmology at the University of Alabama at Birmingham ophthalmology residents and donates time and expertise (UAB), and teaches the intricate surgical procedures of caring for indigent patients. Dr. Parker has served as phacoemulsification and intraocular lens insertion. In Director of the Corneal Service and as Director of the addition, Dr. Callahan lectures on ophthalmic plastic surgery. Residency Training Program in the UAB Department of Dr. Callahan is also very involved in providing ophthalmic Ophthalmology. care in the U.S. and countries worldwide, where medical care is not readily available.

V. HUGO MARX, III, PAUL S. STERNBERG, JR., MD, LARRY A. DONOSO, MD, PhD, JD, serves as Treasurer and has been a serves as Director of Research Funding serves as Emeritas Director of Research member of the IRRF Board since 2004. for the Foundation in addition to his Education and continues to provide Mr. Marx operates several corporations, many other responsibilities at Vanderbilt advice to the Foundation Board. Dr. which represent various industries, University in Nashville, Tennessee, where Donoso has over four decades of bench including health care, investment he is Associate Dean for Clinical Affairs and clinical research experience, which banking and venture capital. Through and Assistant Vice Chancellor for Adult adds an important component to the his numerous businesses, Mr. Marx has Health Affairs at the Vanderbilt School combined talents of the IRRF Board of provided charitable donations as medical of Medicine. He also serves as professor Directors. Holding degrees in chemistry, supplies, food and support items used in and chairman of the Department of experimental biology, biochemistry/ multiple, extreme emergency situations in Ophthalmology and the Vanderbilt Eye biology, medicine and law, allowed Dr. and outside the U.S. Institute. With a special interest in Donoso to serve as Scientific Director age-related macular degeneration, Dr. when the Foundation was newly formed Sternberg oversees a cell biology and and served as a steadfast member of the biochemistry laboratory that carries out board for 17 years. studies into the causes of the disease. Table of Contents 2017 Loris and David Rich Postdoctoral Scholar...... 4

2018 Loris and David Rick Post-doctoral Scholar...... 5

2017 Alston Callahan, MD Postdoctoral Scholar...... 6

The 2017 Weisenfeld Award...... 8

RPB/IRRF Catalyst Award for Innovative Research...... 10

2018 Alston Callahan, MD Postdoctoral Scholar...... 12

About the N-myc regulates growth and fiber cell differentiation Cover Photo in lens development...... 13 The cover photo is a high- resolution confocal image of IRRF Grants 1998–Present...... 14 the nerve fiber layer of a mouse retina taken by Mr. Gabriel Collaborations That Support Advocacy...... 16 Luna, University of California Santa Barbara, California, USA. The image received Honorable Partnerships That Produce Impactful Results...... 17 Mention at the International Digital Imaging Competition Collaborations That Provide Sustained Research Funding....18 sponsored by Olympus BioScapes.

The IRRF and Prevent Blindness...... 20

Current Eye Research...... 21

Southeastern Vision Research Conference...... 22

The Eivor and Alston Callahan, MD, Endowed Chair...... 24

UAB Connections...... 25

The Lasker/IRRF Initiative for Innovation in Vision Science...... 26 4 | IRRF Biennial Report 2017 Loris and David Rich Postdoctoral Scholar Recipient ally Ong, MD, the 2017 Loris After graduating from Duke, she the AAO (American Academy of and David Rich Postdoctoral returned to Southeast Asia to Ophthalmology). Scholar, was born and raised in begin medical school at Duke- Currently, Dr. Ong is working on SBatu Pahat, a small town in Malaysia, National University of Singapore a two-year vitreoretinal surgery and attended Duke University in Graduate Medical School, clinical fellowship at the Wilmer Durham, North Carolina, on a full where she was granted the Goh Eye Institute at Johns Hopkins scholarship awarded to top Malaysian Foundation Research Award in University School of Medicine. high school students, graduating support of a research year in with distinction in Biology with a Dr. Scott Cousin’s laboratory at Dr. Ong was sponsored and Neuroscience concentration in 2007. the Duke Eye Center. Following mentored by Cynthia A. Toth, PhD, While at Duke, Ong completed her graduation from medical school, Duke University Department of senior thesis as a Howard Hughes Dr. Ong completed a transitional Ophthalmology during her time as Biology Forum Research Fellow year internship at a Tufts Medical an IRRF-Rich Scholar. and was a selected member of the Center affiliated hospital before Hart Leadership Program, the first joining the Duke Eye Center endowed leadership program for as an ophthalmology resident. undergraduates in the country. After performing a complex review of patient cases of Coats’ disease treated at Duke over the past 20 years, she was invited to present her work at ARVO (Association for Research in Vision and Ophthalmology) and

PROJECT TITLE: Retinal Imaging with Optical Coherence Tomography in Neonatal Brain Injury to Evaluate and Improve Visual and Neurologic Outcomes.

Sally Ong IRRF Biennial Report | 5 2018 Loris and David Rich Post- doctoral Scholar Award Recipient Tia J. Kowal, PhD fter graduating from that her PhD training at Lehigh Lehigh University, University spanned multiple Stanford University Bethlehem, Pennsylvania disciplines including cell-material Palo Alto, California Awith a PhD in cell and molecular interactions, cell differentiation, biology, Dr. Kowal began cellular morphology and tissue her postdoctoral career at regeneration. Her research also Stanford University in Palo covered multiple tissue types such Alto, California. Her research as bone, skin, and reproductive interests are to identify the tissues, resulting in a publication subtype(s) of retinal ganglion on primary cilia. (Kowal, Tia cells (RGC) that have primary J., Falk, Matthias M. 2015. cilia and determine what role the Primary cilia on HeLa and other primary cilia is playing in the cancer cells. Cell Biol Int. 2015. function of that specific RGC November; 39(11): 1341-1347.) subtype(s). Dr. Kowal explains

PROJECT TITLE: The Role of Primary Cilia for Retinal Ganglion Cells

Tia J. Kowal 6 | IRRF Biennial Report 2017 Alston Callahan, MD Postdoctoral Scholar Recipient Raji Rajesh Lenin, PhD r. Lenin is a graduate of papers at the ARVO annual the University of Madras, conferences and published Hamilton Eye Institute India, where she received her work in peer reviewed Dher PhD in Biochemistry and journals. She is a recipient of the University of Tennessee Molecular Biology Ophthalmology “Postdoc Achievement Award before coming to the United States. 2017-2018 (junior category)” from Currently, Dr. Lenin is training as the UTHSC Postdoc Association, Health Science Center a postdoctoral researcher at the in appreciation of her consistent University of Tennessee under the commitment and capabilities Memphis, Tennessee mentorship of Dr. Rajashekhar demonstrated in her area of Gangaraju, who describes this research. project as an outgrowth of initial Dr. Gangaraju has high praise studies conducted in his laboratory for Dr. Lenin, which he included and that of Dr. Lenin’s PhD thesis in his support letter during work. Dr. Gangaraju’s studies are the application process for the focused on the investigation of Callahan Scholar Award, “As I cellular and molecular principles have interacted with Dr. Lenin underlying tissue regeneration, over the time of her work here at angiogenesis and inflammation. the University of Tennessee, and Dr. Lenin has distinguished during the process of writing this herself through professional application, I have come to the memberships and conclusion that she will become a academic recognitions. superb researcher in her own right.” She has presented

PROJECT TITLE: Diabetic Retinopathy — Inflammation Passing the Baton to Endoplasmic Reticulum (ER) Stress

Raji Rajesh Lenin IRRF Biennial Report | 7

Journal of Cellular Access the article: Biochemistry: Critical role of endoplasmic reticulum stress in chronic endothelial activation – induced visual deficits in tie2-tumor necrosis factor mice. (October 2018: Volume 119, Issue 10)

Raji Lenin, Peter G. Nagy, Shanta Alli, Department of CONCLUSION: Using a constant endothelial activation Ophthalmology, University of Tennessee Health Science animal model of diabetes, the team showed that chronic Center; Vidhya R. Rao, Department of Molecular inflammatory activation of vascular endothelial cells and Pharmacology and Experimental Therapeutics, hyperglycemia promotes visual deficits downstream of Loyola University; Matthias A. Clauss, Department of endoplasmic reticulum (ER) stress signaling in a feed Cellular & Integrative Physiology, Indiana University; forward loop of proinflammation and loss of endothelial Uday B. Kompella, Skaggs School of Pharmacy and junction proteins. Based on these and the invitro Pharmaceutical Sciences, University of Colorado; analysis, future studies aiming at controlling ER stress Rajashekhar Gangaraju, Department of Ophthalmology pathways and endothelial activation may help protect and Department of Anatomy & Neurobiology, University against disruption of junctional proteins in retinal of Tennessee Health Science Center. endothelial cells and possibly aid in the recovery of This study conducted with IRRF support – Raji Lenin, visual deficits observed in our diabetic retinopathy (DR) PhD, 2017 Alston Callahan, MD Postdoctoral Scholar. model. (below) 8 | IRRF Biennial Report IRRF-Supported Scientist, Johanna M. Seddon, Awarded the 2017 Weisenfeld Award he Mildred Weisenfeld Seddon, the 2017 Recipient of the The International Retinal Research Award for Excellence Mildred Weisenfeld Award,” was Foundation (IRRF) supported in Ophthalmology was published in IOVS, December Dr. Seddon’s project, Evaluation Testablished in 1986 by the 2017, Vol. 58, 6510-6512. of Macular Degeneration Sub- Association of Research in Vision DOI:10.1167/iovs.17-23542 Phenotypes as Biomarkers for and Ophthalmology (ARVO) In 2017, Dr. Johanna Seddon, Progression and Treatment. Her to honor Fight for Sight (FFS) an internationally recognized team evaluated optical coherence founder, Mildred Weisenfeld. ophthalmologist and clinician- tomography (OCT) imaging and Though she lost her sight to scientist, was presented with created a longitudinal imaging retinitis pigmentosa two years the Weisenfeld Award at the database with at least one year before the FFS was begun, annual ARVO meeting held in of follow-up time. The accurate Weisenfeld served as Executive Baltimore, Maryland. As Dr. Jager identification and assessment of Director for 50 years. The states in her lecture, “Dr. Seddon individual AMD subphenotypes, Weisenfeld Award is presented pioneered the field of epidemiology particularly specific subtypes to an individual in recognition and genetic epidemiology in that are observed in early and of distinguished scholarly ophthalmology. She has been at intermediate stages of disease, contributions to the clinical the forefront of scientific research are crucial to the identification practice of ophthalmology. into the leading cause of visual loss of reproducible and intermediate biomarkers of AMD progression. Dr. Johnna M. Seddon and and blindness, age-related macular Dr. Martine J. Jager, whose degeneration (AMD), and the lecture dedicated to Dr. Seddon, determinants and risk factors for “Introducing Johanna M. this disease since the 1980s.”

A manuscript summarizing the results of Dr. Seddon’s study was published in Investigative Ophthalmology & Visual Science, (IOVS): Investigative Ophthalmology & Visual Science Optical Coherence Tomography Features Preceding the Onset of Advanced Age- Related Macular Degeneration

Investigative Ophthalmology & Visual Science (IOVS), Optical Coherence Tomography Features Preceding the Onset of Advanced Age-Related Macular Degeneration, Daniela Ferrara, Rachel E. Silver, Ricardo N. Louzada, Eduardo A. Novais, Gilian K. Collins, and Johanna M. Seddon. Ophthalmic Epidemiology and Genetics Service, Tufts Medical Center, 800 Washington Street #450, Boston, MA 02111. USA. (July, 2017) Invest Ophthalmol Vis Sci. 2017/58:3519-3529. DOI:10.1167/iovs.17-21696 IRRF Biennial Report | 9 This study was conducted with IRRF support — Johanna Seddon. Purpose: Age-related macular Conclusion: Abnormalities in the degeneration (AMD) is a progressive photoreceptors, retinal thickness, RPE, To access this study: disease with multifactorial etiology. and choroid were associated with There is a need to identify clinical higher risk of developing advanced features that are harbingers of AMD. These findings provide insights advanced disease. Evaluations were into disease progression, and may be conducted on morphologic features helpful to identify earlier endpoints for of the retina and choroid on optical clinical studies. coherence tomography (OCT) to determine if they predict progression to advanced disease. 10 | IRRF Biennial Report

RPB/IRRF Catalyst Award for Innovative Research Approaches for Age-Related Macular Degeneration (AMD)

he International Retinal together again in 2017 to launch funding contingent upon Research Foundation a second award, the RPB/IRRF satisfactory progress as judged (IRRF) upholds a mission Catalyst Award for Innovative by a well-respected peer Tto provide financial support for Research Approaches for Age- reviewer. vision research directly and is Related Macular Degeneration, In December 2017, after a committed to sustaining targeted which provided funds to rigorous scientific review researchers who are working on research efforts; however, smaller process rooted in RPB review novel approaches to Age-Related budgets and dwindling donations committees, two Catalyst Award Macular Degeneration (AMD). have placed the non-profit winners were named. sector under intense pressure to AMD is the leading cause of maximize every dollar, making vision loss, affecting more than Collaboration with Research partnerships and collaborations 10 million Americans – more to Prevent Blindness has been an effective way to produce a than cataracts and glaucoma a very positive experience and collective impact. combined, and at present is the joining of our respective considered an incurable eye resources has allowed us to In 2014, the IRRF accepted an disease. The specific factors that extend a significant award, and invitation by Research to Prevent cause macular degeneration we feel confident that worthy Blindness (RPB) to participate are not conclusively known, recipients have been selected. in a funding collaboration and research into this little Both IRRF and RPB are looking that would combine our understood disease is limited by forward to seeing what these collective resources to that of insufficient funding. The RPB/ innovative individuals are able an anonymous donor and a IRRF Catalyst Awards are meant to accomplish with the grant generous bequest received from to act as seed money to high-risk/ money, which we hope will the Sybil Harrington Estate to high-gain vision science research, lead to a significant advance RPB. It was requested that the which is innovative, cutting-edge in AMD research. The funds be used for research that and demonstrates out-of-the box importance of these awards focused on stem cell research thinking. Research related to cannot be overstated, since and AMD. The partnership made both dry and wet forms of AMD there is currently no known three grants possible at $250,000 are supported by this award. cure for this disease. It is over four years. The $300,000 grant is payable hoped this research will further Realizing that there is an ongoing for up to 3 years upon approval our understanding of AMD and need for this type of funding of a 14-month substantive will lead to more options for partnership, RPB and IRRF came progress report, with further treatment. IRRF Biennial Report | 11

Dr. Catherine Bowes Rickman of Duke University School of Medicine, Associate Professor of Ophthalmology and Associate Professor in Cell Biology, whose research interest is the pathobiology of age-related macular degeneration. Her current studies involve the molecular mechanisms underlying the development of age-related macular degeneration, with a focus on development and studies of animal models of AMD, AMD pathogenesis and pre-clinical studies of novel therapies for AMD. Dr. Bowes Rickman has a strong track record of productive research in this field. For the Catalyst Award, she proposes to use unique and relevant models of chronic, dry AMD to test three therapeutic approaches that will shape strategies for targeting the complement pathway versus a combined therapeutic approach targeting both pathways. It is felt this project could have major implications in guiding future human clinical trials in this area.

Debasish Sinha, PhD, University of Pittsburgh School of Medicine, is Professor of Ophthalmology and the recipient of a BrightFocus grant in 2016. Dr. Sinha also has an adjunct faculty appointment at Wilmer Eye Institute, Johns Hopkins. Dr. Sinha’s Catalyst Award proposal aims to develop a treatment for early, dry AMD that works by rejuvenating impaired lysosomal function. (Lysosomes act as the waste disposal system of the cell by digesting unwanted materials.) The committee felt this project is important and innovative because it attempts to target mechanisms that may underlie early stages of AMD – a critical unmet need. Dr. Sinha has exceptional experience in inflammation and, in particular, lysosomal biology, as well as access to high-level collaborators in this area. 12 | IRRF Biennial Report 2018 Alston Callahan, MD

OmarPostdoctoral Moinuddin, r. Moinuddin Scholar is embarking on Recipient years of his medical school training, his first year as a postdoctoral research motivations principally MD University of fellow at the University of focused on ophthalmology as he Michigan Kellogg DMichigan, Kellogg Eye Center in Ann conducted research at Associated Arbor, Michigan, after graduating from Retinal Consultants in Royal Oak, Eye Institute Oakland University William Beaumont Michigan under Dr. George Williams, School of Medicine in Rochester, an internationally recognized Michigan. Moinuddin’s long-term vitreoretinal surgeon and leader in research focus is the development of the field of academic ophthalmology. a comprehensive understanding of Research topics ranged from studying the pathophysiology and treatment of fellow eye outcomes in patients with ophthalmic disease. neovascular age-related macular Early in medical school, Moinuddin degeneration to investigating surgical designed and conducted a longitudinal outcomes using a novel 3D heads-up capstone research project with the surgical display. Cytogenomics Laboratory at Oakland During his year as a Callahan Scholar, University William Beaumont School Dr. Moinuddin will investigate the of Medicine, studying the differential strategy of reprogramming cellular therapeutic response in multiple metabolism as a novel therapeutic myeloma patients with t(11:14) approach for photoreceptor (q13:q32) translocation and subsequent neuroprotection during age-related IGH gene deletion. During the clinical macular degeneration.

PROJECT TITLE: Metabolic Activation to Prevent Photoreceptor Cell Death in a Preclinical Model of Macular Degeneration

Omar Moinuddin N-myc regulates IRRF Biennial Report | 13 growth and fiber cell differentiation in lens development ABSTRACT: yc proto-oncogenes regulate diverse cellular processes during development, but their roles during morphogenesis of specific tissues are not fullyM understood. This study found that c-myc regulates cell proliferation in mouse lens development and previous genome-wide studies suggested functional roles for N-myc in developing lens. The role of N-myc was examined in mouse lens development. Genetic inaction of N-myc in the surface ectoderm or lens vesicle impaired eye and lens growth, while “late” inactivation in lens fibers had no effect. Unexpectedly, defective growth of N-myc-deficient lenses was not associated with alterations in lens progenitor cell proliferation or survival. Notably, N-myc-deficient lens exhibited a delay in degradation of DNA in terminally differentiating lens fiber cells. RNA- sequencing analysis of N-myc-deficient lenses identified a cohort of down-regulated genes associated with fiber cell differentiation that included DNaseIIβ. Further, an integrated analysis of differentially expressed genes inN-myc -deficient lens using normal lens expression patterns of iSyTE, N-myc-binding motif analysis and molecular interaction data from the String database led to the derivation of an N-myc-based gene regulatory network Rodrigo Martins, PhD in the lens. Finally, analysis of N-myc and c-myc double-deficient Dr. Martins is an IRRF-Funded lens demonstrated that these Myc genes cooperate to drive scientist at the Federal University lens growth prior to lens vesicle stage. Together, these findings of Rio de Janeiro, where he is an provide evidence for exclusive and cooperative functions of Myc Assistant Professor. His funded transcription factors in mouse lens development and identify project, Smc1 and the Cohesin novel mechanisms by which N-myc regulates cell differentiation Complex in Retinal Development during eye morphogenesis. and Disease: A New Mouse Model of Photoreceptor Degeneration, TERMS: MYC — an immediate early response gene downstream of has resulted in a published paper many ligand-membrane receptor complexes (Armelin et al., 1984; Kelly et in Developmental Biology, “N-myc al., 1983) binding to 10%–15% of genomic loci in mammals. regulates growth and fiber cell Oncogene — defined as a gene that encodes a protein that is capable differentiation in lens development.” of transforming cells in cultures or inducing cancer in animals. Morphogenesis — can be defined as the processes that are responsible for producing the complex shapes of adults from the simple ball of cells that derives from division of the fertilized egg. (On- line Medical Dictionary, © 1997–98 Academic Medical Publishing & CancerWEB). To read this paper in its entirety, please follow the link: Wright State University, $199,500

Baylor College of Medicine, $729,416 Washington University, Radboud Vanderbilt University , $1,191,605 $477,348 University Case School of Medicine, $299,451 Yale University, Medical Various Institutions, $854,932 $295,000 Center, University of Western Sydney, $200,000 $99,249 Columbia University , $200,000 AAO, $253,600 Cornell University , $334,500 Research to Duke University, $360,520 University of Texas-Galveston, $400,000 Prevent Erasmus Medical Center, $276,787 Blindness, Fight for Sight, $121,850 University of Tennessee, $924,500 $459,500 Georgia Health & Science University, $100,000 University of Utah, $195,500 Kasindo Eye Clinic, $76,938 Harvard University , $200,000 University of Schleswig-Holstein, $100,000 Indiana University, $557,100 Institute of France, $94,000 University of Rio de Janeiro, $124,034

University of Pennsylvania, $557,000

University of Pisa, $150,900 University of Oklahoma, $100,000

University of New Mexico, $200,000

University of Michigan, $170,000

University of Miami, $100,000 Lasker Foundation, $4,047,262

University of Massachusetts , $395,393 The Jackson Laboratory, $302,425

University of Kentucky, $405,610 University of Iowa, $430,700 University of Chicago, $99,835 Massachusetts Eye & Ear Inﬁrmary, $93,812 University of California Santa Barbara,- $167,100 University of California-San Diego, $99,995 Northeast Ohio University , $200,000 University of California-Irvine, $99,494 Purdue University , $235,000 St. Jude's Hospital, $100,000 University of California-Davis, $400,000

Tufts Medical Center, $200,000 University of California-Berkley, $100,000

University of Arizona, $200,000

University of Alabama at Birmingham, $4,080,854

Grand Total All Years $22,915,642 Various Institutions Include all grants less than $75,000

14 | IRRF Biennial Report Wright State University, $199,500 The International Retinal Research Foundation Baylor College of Medicine, $729,416 Washington University, Radboud Vanderbilt University , $1,191,605 Grants 1998 – Present $477,348 University Case School of Medicine, $299,451 Yale University, Medical Various Institutions, $854,932 $295,000 Center, University of Western Sydney, $200,000 $99,249 Columbia University , $200,000 AAO, $253,600 Cornell University , $334,500 Research to Duke University, $360,520 University of Texas-Galveston, $400,000 Prevent Erasmus Medical Center, $276,787 Blindness, Fight for Sight, $121,850 University of Tennessee, $924,500 $459,500 Georgia Health & Science University, $100,000 University of Utah, $195,500 Kasindo Eye Clinic, $76,938 Harvard University , $200,000 University of Schleswig-Holstein, $100,000 Indiana University, $557,100 Institute of France, $94,000 University of Rio de Janeiro, $124,034

University of Pennsylvania, $557,000

University of Pisa, $150,900 University of Oklahoma, $100,000

University of New Mexico, $200,000

University of Michigan, $170,000

University of Miami, $100,000 Lasker Foundation, $4,047,262

University of Massachusetts , $395,393 The Jackson Laboratory, $302,425

Tufts Medical Center, $200,000 University of California-Berkley, $100,000

University of Arizona, $200,000

University of Alabama at Birmingham, $4,080,854

IRRF Biennial Report | 15 16 | IRRF Biennial Report Partnerships That Produce Impactful Results: On March 21, 2018, the think collectively about how to collaborate when appropriate, best support scientific research thereby increasing the impact IRRF joined more than related to eye health and to that any one organization can 30 other organizations to maximize the impact of private have on its own. A focus for this funding in this area. meeting was the collaborations of participate in a convening Research to Prevent Blindness organizations over the past year (RPB) has hosted the convening that have led to successful projects of vision funders in since 2013 with co-sponsorship with the potential to impact the from the Glaucoma Research field of vision research that may Washington D. C. for the Foundation, E. Matilda Ziegler ultimately increase treatments, fifth consecutive year. Foundation for the Blind, preventives and cures for vision EyeSight Foundation of Alabama, loss and eye diseases. Sandra International Retinal Research Blackwood of the IRRF reported This year’s high-level meeting, on the partnership between that Foundation (IRRF), Lighthouse “Vision Research Funding organization and RPB to provide Guild, and Richman Associates, Partnership V: The Eye in the two awards, the RPB/IRRF Age of Artificial Intelligence LLC (in-kind). Catalyst Award for Innovative (AI),” provided leaders of A major goal of the meeting Research Approaches for Age- organizations that fund vision is to create a community of Related Macular Degeneration research the opportunity to vision research funders that can (AMD). IRRF Biennial Report | 17 Collaborations That Support Advocacy: Federal funding for vision ince 2010, the International On March 22, 2018, NAEVR research is vital, as the Retinal Research Foundation hosted a Private Vision Research has been an active partner Funding Foundations Advocacy National Eye Institute Swith the National Alliance For Eye Day with attendees of the previous And Vision Research (NAEVR), an day’s Fifth Annual Vision Research (NEI) within the National advocacy organization comprised Funding Partnership event, hosted Institutes of Health (NIH) of a coalition of 55 professional, patient and consumer, and by Research to Prevent Blindness is responsible for funding industry organizations. NAEVR’s (RPB). Advocates described the sight-saving and sight- goal is to achieve the best eye importance of their organizations and vision care for all Americans to the state/district and their restoring vision research through advocacy and public role in providing early-stage and nationwide. education for eye and vision bridge funding for investigators. research sponsored by the IRRF Executive Director, Sandra National Institutes of Health Blackwood met with staff (NIH) and its National Eye Institute (NEI), Department of members for U.S. Senators Doug Defense (DOD), Department of Jones (D-AL) and Richard Shelby Veterans Affairs (VA) and other (R-AL), as well as Gary Palmer, U. federal agencies. S. Representative from Alabama.

Sandra Blackwood (International Retinal Research Foundation), left, and Torrey DeKeyser (EyeSight Foundation of Alabama), right, with Katie Campbell in the office of Senator Doug Jones (D-AL) 18 | IRRF Biennial Report

Collaborations That Provide Sustained Research Funding 2017 — John T. Pena, MD, PhD, Weill Cornell Medical College for his work in diabetic retinopathy. Grant Title: Human ocular fluid contains an intercellular communication system of endogenous exosomes. Summary: The vitreous humor of the eye is a clear gel-like structure comprised of collagen and water and fills the back of the eye. Traditional thinking has been that the vitreous is biologically inactive. Dr. Pena’s study showed a dense organized network of extracellular vesicles (EVs) in the human vitreous. However, attempts to image vitreous EVs in whole mount or tissue sections resulted in no evidence of EVs. Yet, electron microscope (EM) studies and nano-particle tracking analysis proved that millions of EVs exist in the vitreous. To solve this discrepancy and visualize the native anatomy of vitreous EVs a hypothesis emerged that the nanometer sized EVs were lost during tissue processing secondary to reversible formalin-fixation. Therefore, this team developed an innovative fixation technique to enable visualization of vitreous EVs in situ. In addition to identifying the vitreous EVs, it was proven that vitreous EVs are a highly potent vector that can be loaded with synthetic siRNAs or proteins, and subsequently transfects retinal cells in vitro and in vivo. The team has shown that vitreous EVs can be used as a vector to efficaciously deliver therapeutic recombinant proteins to tissues like the retina and choroid. Current and Future Academic Plans: Dr. Pena’s academic plans are to continue to grow and become a productive physician-scientist. He is currently an Assistant Professor of Ophthalmology at Weill Cornell Medicine and Principal Investigator of the laboratory. Dr. Pena plans to use his training from the clinic and basic sciences to ask pertinent questions that remain a challenge in vision research. He hopes to provide straightforward solutions that can be translated to benefit his patients and will take the next few years as an opportunity to develop strong academic relationships with his mentors and students.

2018 — Jordan Greco, PhD, University of Connecticut, for his work in the characterization of an ion-mediated protein-based retinal implant. Dr. Greco obtained his PhD in physical chemistry at the University of Connecticut in 2015. Under the mentorship of Dr. Robert Birge, Dr. Greco’s graduate thesis work primarily involved the investigation of the structure and function of photoactive proteins, using both spectroscopic and quantum mechanical approaches. Much of his work has contributed towards the application of the protein bacteriorhodopsin into photonic and biomimetic devices, such as protein-based optical memories and processors, photovoltaic cells, and the retinal implant developed by LambdaVision, Inc. Concurrent with his work on bacteriorhodopsin, Dr. Greco has contributed to numerous computational analyses for the excited state of behavior of heterocyclic conjugated compounds, (e.g., porphyrin, chlorins, and corroles), carotenoids (e.g., peridinin), and other polyene-based chromophores rooted in biological systems. Dr. Greco has presented this work to international audiences and he continues to remain active in the field via several multidisciplinary collaborations. (Reprinted from Crunchbase: www.crunchbase.com/ person/jordan-greco). IRRF Biennial Report | 19

oday’s vision scientists face many funding institutions has made it possible to accomplish this challenges making it imperative that all support while producing a collective impact. Since 2013, New options are available to them. Similarly, in order York-based Fight For Sight (FFS) and the IRRF have Tto ensure continued funding for young scientists who combined resources to provide an annual funding are developing their independent research projects, award: FFS -The International Retinal Research the IRRF must maximize every dollar. The formation Foundation Grant-in-Aid Award that is offered and of partnerships and collaborations with outstanding administered by FFS. Related Story… ince joining the research Dr. Birge’s research group, Nicole procedures and quality control group of Dr. Robert Birge Wagner, PhD and Jordan Greco, measures. Moreover, his research in 2009, University of PhD.) efforts helped to direct critical SConnecticut, Jordan Greco has Dr. Greco’s graduate thesis proof-of-concept experiments been actively involved in the work influenced the design that investigated the efficacy of research and development that and development of the retinal the retinal implant architecture. has led to the creation of the implant construct and the Recently, the company’s robotic protein-based retinal implant manufacturing techniques used system to manufacture films that and the commercialization to produce the prosthetic. As could cure blindness was brought of this technology through Chief Scientific Officer, Dr. Greco to the International Space Station LambdaVision. (LambdaVision is is responsible for manufacturing U.S. National Laboratory by the led by University of Connecticut the retinal implants and SpaceX Dragon spacecraft. alumni and former students in establishing standard operating 20 | IRRF Biennial Report The International Retinal Research Foundation and Prevent Blindness:

he IRRF was pleased to sponsor the 2018 program development and replication. It also serves Focus on Eye Health National Summit: as a strong springboard to release important new Research to Impact, held in Washington, D. public health information, including prevalence TC. This event has become a key venue to elevate data with Vision Problems in The U.S., economic the national dialogue around vision and significant information with Cost of Vision Problems, and public health issues such as surveillance, access, forecasting data on the potential future prevalence prevention messaging, service integration, and and costs with The Future of Vision. IRRF Biennial Report | 21 Current Eye Research ApoA-l Mimetic Purpose: Accumulation of Peptide 4F lipoprotein-derived lipids including Reduces Age- esterified and unesterified cholesterol Related Lipid in Bruch’s membrane of human eyes is Deposition in a major age-related change involved Murine Bruch’s in initiating and sustaining soft drusen Membrane in age-related macular degeneration and Causes (AMD). The apolipoprotein (apo) A-l Its Structural mimetic peptide 4F is a small anti- Remodeling. inflammatory and anti-atherogenic (October 2017) agent, and potent modifier of plasma membranes. This team evaluated the effect of intravitreally-injected 4F on murine Bruch’s membrane. Martin Rudolfa, Armin Mir Mohi Sefata, Yoko Miuraa, Aysegül Turaa, Walter Raaschb, Mahdy Ranjbara,c, Conclusion: The research Salvatore Grisantia, Zouhair Aherrahroud, Anna demonstrated a highly effective Wagnera, Jeffrey D. Messingere, David Garberf, GM pharmacological reduction of Anantharamaiahf,g, and Christine A. Curcioe. esterified cholesterol (EC) and aDepartment of Ophthalmology, University of Lübeck, restoration of Bruch’s membrane Germany; bDepartment of Experimental and Clinical ultrastructure. The apoA-l mimetic Pharmacology and Toxicology, University of Lübeck, peptide 4F is a novel way to treat a Germany; cLaboratory for Angiogenesis & Ocular critical AMD disease process and Cell Transplantation, University of Lübeck, Germany; thus represents a new candidate for dInstitute of Integrative and Experimental Genomics, treating the underlying cause of AMD. University of Lübeck, Germany; eDepartment of To read this paper in its entirety, Ophthalmology, University of Alabama at Birmingham, f please scan the QR code below: Birmingham, Alabama, USA; Atherosclerosis Research Unit, University of Alabama at Birmingham, Birmingham, AL, USA; gDepartment of Medicine, Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL, USA This study was supported by IRRF Funds;Martin Rudolf and Christine A. Curcio. 22 | IRRF Biennial Report Southeastern Vision Research Conference Fosters Exchange of Scientific Findings: The IRRF recently collaborated with the Birmingham brought together vision scientists University of Alabama at Birmingham (UAB) from Vanderbilt University Medical Center, the Department of Ophthalmology and Visual University of Alabama at Birmingham, and Emory Sciences by sponsoring the second annual University to foster an exchange of ideas among Southeastern Vision Research Conference the groups, each with its own unique strengths. (SEVRC) to celebrate and share excellence in The next SEVRC will be held in 2020 at Emory vision science. The two-day seminar held in University in Atlanta, Georgia. IRRF Biennial Report | 23 Southeastern Vision Research Conference Fosters Exchange of Scientific Findings: Constance “Connie” Cepko, PhD, Bullard Professor UAB members of the program committee, noted, of Genetics and Neuroscience at Harvard “collaboration and communication is the road Medical School, and a pioneering developmental forward on finding ways to preserve and restore and molecular neurobiologist, gave the keynote good vision.” lecture, “Cell Fate Determination in the Retina and This year’s conference had a record number Strategies to Prolong Vision Using Gene Therapy.” of attendees with 195 registrants, 87 poster Christine A. Curcio, PhD and Alecia Gross, PhD, presentations, and 22 speakers.

Left to right: Dr. Alecia Gross, Associate Professor, UAB School of Optometry; Dr. Connie Cepko, Harvard Medical School; Dr. Christine Curcio, White-McKee Endowed Professor, UAB Department of Ophthalmology and Visual Sciences. 24 | IRRF Biennial Report

The Eivor and Alston Callahan, MD, Endowed Chair in Ophthalmology University of Alabama at Birmingham School of Medicine

Birmingham, Alabama Maria Grant, MD is the inaugural holder of the Eivor and Alston Callahan, MD Endowed Chair in Ophthalmology. Dr. Grant’s laboratory is interested in understanding the functional process of hematopoietic stem cells, and focusing on understanding how to best utilize human embryonic stem cells for vascular repair. The ability to repair vascular damage could have a profound impact on a large number of retinal diseases. The best possible approach for repair is targeted gene expression to force selective differentiation, therefore offering novel therapeutic possibilities for tissue repair throughout the body. Dr. Grant (above) earned her medical degree from the University of Florida, where she also completed her residency. She completed a research fellowship in the Division of Endocrinology & Metabolism at the University of Florida and a research fellowship at The Wilmer Eye Institute at Johns Hopkins University. The International Retinal Research Foundation established The Eivor and Alston Callahan, MD, Endowed Chair in Ophthalmology to support the work and mission of the Department of Ophthalmology through the recruitment and /or retention of a distinguished ophthalmologist who specializes in retina care. It is most fitting that this endowment bear the names of Dr. Alston Callahan and Mrs. Eivor Callahan, as recognition of their extraordinary legacy within the Birmingham community and the field of vision health. Dr. Callahan began the facility now known as The UAB Callahan Eye Hospital. Additionally, he was integral in the establishment of the UAB Department of Ophthalmology and served as the first Chairman. IRRF Biennial Report | 25

UAB CONNECTIONS: Dedicated to the well-being of visually challenged individuals. University of Alabama at Birmingham (UAB): lonely. Connections helps equip patients and families The IRRF is pleased to continue its support of with tools to focus on what they can do, rather than UAB Connections, an innovative, facilitator-led what they cannot do. psychoeducational support group for patients and their A generous donation to the International Retinal families living with vision loss. This program serves Research Foundation by Mrs. Camilla Huxford has Alabamians with various eye diseases unlike any enabled the IRRF to supply funding for UAB Connections other eye care facility or traditional eye care efforts in for the next fiscal year. Mrs. Huxford’s gift will also Alabama or across the nation by treating the “whole support retinal research through grants made by the person” versus the eye disease alone. When nothing IRRF. It is with sincere appreciation and gratitude that further is achievable medically or surgically, the impact we acknowledge this support. and adjustment process can be quite frightening and

Right: Allie McBrayer, Dr. Laura Dreer, Director, UAB Connections; Sandra Blackwood, IRRF Executive Director; and Molly Cox, Connections Program Director. 26 | IRRF Biennial Report The Lasker/IRRF Initiative for Innovation in Vision Science: A Partnership Between the Albert and Mary Lasker Foundation and the International Retinal Research Foundation he Lasker/IRRF Initiative has been a successful Lasker and IRRF are thrilled with the achievements collaboration, inspired by the IRRF Board’s of the Initiative, thanks to the tremendous idea that, together, the two Foundations could contributions of more than 300 scientists in Taccelerate the understanding of retinal degenerative multidisciplinary fields who discussed impediments diseases using multidisciplinary scientific, technological to progress, debated ways to solve vexing issues and and engineering approaches. Over the ten-year span developed novel and creative methodologies that are IRRF provided support of more than $4 million for four now driving important research advancements. individual projects in glaucoma, diabetic retinopathy, The IRRF Board of Directors met at the restoring vision to the blind and amblyopia, plus a five- 2018 Association of Research in Vision and year follow-up assessment of the initial glaucoma study. Ophthalmology (ARVO) in Honolulu, Hawaii and were able to attend special interest sessions supported by the Initiative. The group took this opportunity to discuss the outcome of the project with John Dowling, MD, Gordon and Llura Gund Professor of Neurosciences, Harvard Medical School, who served as Chairman of the Initiative.

Left: Lasker Foundation President, Claire Pomeroy, PhD, Presented Michael A. Callahan, MD, President of the IRRF, a Resolution Commemorating the Partnership. IRRF Biennial Report | 27

“The Axon and New Therapies.” Presented by David J. Calkins, PhD, “Astrocytes and Glaucomatous Neurodegeneration Axon- The Denis M. O’Day Professor of Ophthalmology and Visual Sciences, Astrocyte Interactions.” Presented by Leonard A. Levin, Vice-Chairman and Director of Research, Vanderbilt Eye Institute, MD, PhD, Professor and Chair of Ophthalmology, McGill Vanderbilt University Medical Center, Nashville, Tennessee. University Health Centre, Montreal, Canada.

From Left to right: John S. Parker, MD, IRRF Vice President; V. Hugo Marx, III, IRRF Treasurer; Claire Pomeroy, PhD, Lasker Foundation President; Michael A. Callahan, MD, IRRF President; John Dowling, MD, Lasker/IRRF Initiative for Innovation in Vision Science Chairman; Karen Wright, Initiative Program Administrator; Sandra Blackwood, IRRF Executive Director; Paul Sternberg, Jr., MD, IRRF Director of Research Funding.

Following is an excerpt from and Sandra Blackwood, the Executive remarks by John Dowling, MD, Director of the IRRF, as well as the staffs of the National Academy of Sciences’ who chaired the Initiative. J. Erik Jonsson Center in Woods Hole, “…I would like to thank not only the panel Massachusetts, where workshops were held members who participated in the special for all the studies, and the Janelia Research interest groups this year but also everyone Center of the Howard Hughes Medical who contributed to the Initiative. We Institute where the plenary sessions were estimate that over 300 individuals attended held. at least one of the 20 meetings held over the Most importantly, the Initiative could 10 years, and many participated in three never have happened were it not for the or more meetings. Those involved were vision and generous financial support of the John Dowling, MD exceptionally enthusiastic and most willing International Retinal Research Foundation to contribute, making the Initiative an and the enthusiasm of the Albert and enormous pleasure to chair. Mary Lasker Foundation to undertake this Special thanks go to Karen Wright, the remarkable and productive collaboration. Program Administrator for the Initiative, We are all very grateful.” 28 | IRRF Biennial Report

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