John D. Ash, Ph.D., an associate professor in the University of Florida College of Medicine’s Department of Ophthalmology, discusses his research on the pathways involved in the loss of sight due to inherited retinal degenerations.
Dr. Ash’s research is focused on both understanding the cause of blindness due to retinal degeneration and developing therapies to prevent loss of sight. His research is relevant to inherited retinal degenerations such as retinitis pigmentosa, cone-rod dystrophies, LCA, or age related macular degeneration. His most recent studies have shown the important contribution of endogenously expressed cytokines such as leukemia inhibitory factor (LIF). His work has shown that these cytokines are expressed under conditions of stress, and that the increased LIF is important to prevent or delay photoreceptor or RPE cell death under chronic stress conditions, including inherited mutations known to cause blindness. By using mouse genetic engineering, his lab has demonstrated that loss of the LIF receptor, gp130 or it’s signaling intermediate STAT3, results in accelerated retinal degeneration
The results from this work have broad implications in the understanding of human inherited retinal degeneration. In humans, disease-causing genes are present before birth; however patients inheriting those mutations that cause retinitis pigmentosa or age related macular degeneration typically do not develop disease for 40 to 80 years. Dr. Ash’s work suggests that LIF and its receptor gp130 keep cells alive and functioning, and serve to delay the onset and progression of disease. Variation in efficiency of this internally protective activity could also be a partial explanation of why family members who inherit the same mutation can have a wide range in the age of onset and severity of disease. This work has led to the identification of drug targets to promote cell survival, and has led to the development of several gene therapy approaches to specifically enhance the survival of photoreceptors and RPE which are now being tested in models of disease.
Dr. Ash is the Francis M. Bullard Eminent Scholar Chair in Ophthalmic Sciences, and is an Associate Professor of Ophthalmology, College of Medicine, at the University of Florida.
Dr. Ash received his Ph.D. from the Ohio State University Biochemistry Program in 1994 and completed postdoctoral training in the Cell Biology Department at Baylor College of Medicine, in Houston, Texas, and began his faculty career at the University of Oklahoma Health Sciences Center, Oklahoma. Dr. Ash is also a Visiting Professor at the Dalian Medical University, Dalian China. Dr. Ash has written and published 60 manuscripts including research articles, book chapters and invited reviews, and has edited four books. Dr. Ash’s research is focused on mechanisms of retinal degeneration and neuroprotection, with a focus on degeneration of photoreceptors and the RPE. This work also has a strong translational component and has led to the creation of two new neuroprotective drugs and the identification of 3 novel pathways to induce neuroprotection pharmacologically. Dr. Ash’s work has led to intellectual disclosure filings, and the filing of one U.S. Patent Application. He is currently an Executive editor for Experimental Eye research and a Scientific Review Editor for Molecular Vision. Dr. Ash is an active reviewer for these journals as well as Investigative Ophthalmology & Visual Science. In 2009, Dr. Ash received a research award from Hope for Vision, and in 2010 he received a Lew R. Wasserman Merit award from Research to Prevent Blindness, Inc. Dr. Ash has received grants from the National Institutes of Health, the Foundation Fighting Blindness, Research to Prevent Blindness, Inc., Hope for Vision, and the American Diabetes Association. Dr. Ash has served on the Program and Advocacy committees of the Association for Research in Vision and Ophthalmology. Dr. Ash has served on the scientific review panel for Fight For Sight (2005-2008) and is currently serving on the Scientific Advisory Board of the Foundation Fighting Blindness (Columbia, MD) where he chairs the review committee on Novel Medical Therapies Program. He also serves on the scientific review panel for the Macular Degeneration program of the BrightFocus Foundation (formerly the American Health Assistance Foundation, Clarksburg, MD).