The Curing Retinal Blindness Foundation Board of Directors works with the Scientific Advisory Team to make decisions of funding research for degenerative retinal disease.
Dr. Maumenee is director of the Ocular Genetics Laboratory and serves as a consultant for the Pediatric Ophthalmolgy and Adult Strabismus Service. She has had a long and successful career as a clinician scientist. Dr. Maumenee began her medical studies in Germany and continued postdoctoral training in medicine, medical genetics and ophthalmology at the University of Geneva, the University of Hawaii and the Wilmer Ophthalmological Institute at Johns Hopkins University. While on the Wilmer Institute faculty she founded and directed the Johns Hopkins Center for Hereditary Eye Diseases. She is the co-founder of the International Society for Genetic Eye Diseases. Dr. Maumenee has also served as an active consultant to the John F. Kennedy Institute for the Visualy and Mentally Handicapped Children. Her clinical and research interests are in the classification and management of hereditary ocular diseases, population genetics, and molecular genetics. Dr. Maumenee has published over 300 journal articles and serves as section editor for birth defects and genetic diseases for the British Journal of Ophthalmology. She has received awards from the American Academy of Ophthalmology, the National Marfan Foundation, Women in Ophthalmology and the Internation Society of Genetic Genetic Eye Diseases. She joined the Illinois Eye and Ear Institute faculty in 2008. Dr. Maumenee is board certified in ophthalmology and medical genetics.
Dr. Scribner is Senior Vice President of Medical and Regulatory Affairs at RRD International, LLC. Dr. Scribner is a board certified physician in internal medicine and has direct experience running large clinical programs. He joined RRD from Intarcia Therapeutics, where he was the Vice President of Regulatory and Quality Affairs and Chief Regulatory Officer. Previously, Dr. Scribner was Chief Regulatory Consultant for Quintiles Consulting, where he developed and wrote numerous NDA, BLA, IND, IDE, 510(k), PMA, and MAA applications. Prior to Quintiles Consulting, Dr. Scribner spent 10 years at FDA, where he held a variety of positions and was involved in reviewing products regulated by the Center for Biologics. Dr. Scribner holds an MD from the University of Colorado College of Medicine, an MBA from the University of Maryland College of Business and Management, and a BA in biology from Grinnell College.
Dr. Selzer’s research is in the area of regeneration in the central nervous system, using the spinal cord of the sea lamprey as a model for determining the molecular mechanisms that underlie regrowth of axons after injury. Early on, his laboratory demonstrated that spinal cord axons regenerate selectively in their correct paths and make physiologically functioning synapses specifically with correct neuron types. The spinal-projecting neurons in the brainstem are very heterogeneous in their regenerative abilities. Those that are bad regenerators downregulate neurofilament (NF) mRNA expression permanently after axon section, whereas good regenerators show recovery of NF expression. Since the regenerating axon tips lack filopodia, have sparse F-actin and are densely packed with NFs, the Selzer lab is testing whether NFs are involved in the mechanism of regeneration. They are now using in vivo micro-imaging and two-photon microscopy to distinguish axons that are actively regenerating from those that are static or retracting and observe their responses to pharmacological and molecular manipulations. Using these microimaging techniques, they have found that axon regeneration is intermittent and that increasing cAMP activity increases the velocity of axon regeneration but not the time spent in forward movement, as opposed to stasis or retraction. Another characteristic of bad regenerating neurons is their upregulation of receptors for certain guidance molecules after axotomy. In other systems, these receptors act as “dependence receptors,” activating an apoptosis cascade when they are not bound by their ligand. With Dr. Michael Shifman, Dr. Selzer has found that the ligands for these receptors are down-regulated transiently near the site of spinal cord transection, and that the bad-regenerating neurons undergo delayed apoptotic cell death, i.e., they are TUNEL and caspase 3 positive and eventually disappear. Thus, the lab is now testing whether certain neurons are bad regenerators because at the time of assessment, they are already undergoing very slow dependence receptor-mediated apoptosis.
Dr. Selzer is the recipient of numerous grants and awards from the NIH and other government and voluntary organizations and has served on peer review panels for the NIH, the Department of Veterans Affairs and the National Multiple Sclerosis Society.
Stephen Tsang, M.D., Ph.D.’s research efforts are to find new treatments for photoreceptor degeneration in retinitis pigmentosa (RP), age-related macular degeneration (AMD) and related retinal dystrophies, the most common forms of degenerative disease in the central nervous system and have profound impact on quality of life. Over 9 million Americans are affected with photoreceptor degenerations, far exceeding the number with Alzheimer disease. Inherited forms of photoreceptor degeneration affect about one in 2000 people. Presently there is no cure.
RP is the most common cause of inherited blindness, named for the increased pigmentation that appears in the areas of retinal cell death during late manifestation of the disease. Initial symptoms include night blindness, due to the death of rod photoreceptor cells – the light-sensing neurons at the peripheral retina – resulting in “tunnel vision.” In later stages, RP destroys cone photoreceptor cells in the macula, responsible for fine central vision. One in ten Americans is a carrier for a defect in one of the 180 genes associated with RP. Our research has illuminated the mechanisms by which the phosphodiesterase (PDE6) signaling network regulates rod and cone survival. Defects in the PDE6 gene account for approximately 75,000 yearly cases of RP worldwide.
In related research initiatives, we study and manipulate photoreceptor degeneration gene expression in mice, which closely parallels similar conditions in humans. Their goal is to control the expression of this faulty PDE6 gene by using inducible gene targeting that allows the activity of a gene in a specific tissue to be disrupted at any time during the life of a mouse. By following the effects of the genetic abnormality after the photoreceptors have fully developed, they hope to gain an understanding of the early events controlling photoreceptor signaling and degeneration in mice, which could lead to new drug targets for the prevention or delay of human retinal degenerations.
Gaining temporal and spatial control of gene expression is essential for the elucidation of gene function in the whole organism. The reagents that we develop can be built into gene therapy vector to provide temporal and spatial control of gene expression of any therapeutic gene. An inducible gene targeting system can be used to address several previously unapproachable problems in sensory biology as well as gene therapy.
Furthermore, we believe that cell transplantation in the human retina has the potential to restore lost vision and provide treatment for advanced stages of retinal degeneration featuring significant photoreceptor neuronal loss, noting that a major obstacle for this approach is the ability to produce sufficient patient specific photoreceptor cells for transplantation. Adult retinal stem cells, which reside in the ciliary body of the adult human eye, are one potential source of photoreceptors. Fish regenerate retinal neurons from a population of stem cells that are intrinsic in the ciliary body, which surrounds the lens of the eye and maintains proper pressure in the eyeball; these cells reside within the differentiated retina throughout the lifetime of the animal. The progeny of fish stem cells can divide and migratory progenitors are the antecedents of photoreceptor precursors. It is these intrinsic adult retinal stem cells that allow the fish to regenerate photoreceptor neurons spontaneously when existing neurons are killed. Stem cell transplantation therefore has the potential to restore lost vision and provide treatment for advanced stages of retinal degeneration even in cases of significant photoreceptor loss in humans.
Our research paves the way toward
“retinoplasty,” reconstruction of interfaces between photoreceptors and their environment after the onset of retinal degeneration. Our approach involves the culture of human retinal stem cells from the ciliary body in eye-bank globes, and using those cultured cells to determine the combination of transcription factors involved in regulating their proliferation and differentiation into light-sensing photoreceptor neurons. These experiments will identify the effectors regulating human retinal stem cell differentiation and proliferation, as well as testing the ability of in vitro generated stem cells to repopulate the diseased retina. Future applications may include patient-specific stem cells obtained from fine-needle aspiration of their ciliary bodies in the operating room. Based on our findings, we foresee the ability to manipulate the patients’ own stem cells to cure their specific disease. This approach will solve the problem of limited supply of allograft rejection by using a patient’s own cells.