Neena Haider, PhD
University of Nebraska
Project: Research into genetic modifiers of retinal degenerations
Summary: Dr. Haider’s research uses molecular genetics to identify and characterize genes important in vision loss. The goal of her lab is to identify novel genes associated with retinal disease, determine the gene networks that regulate retinal stem cells, and identify modifier genes that can prevent retinal degeneration and restore vision in degenerating retinas. The goal of this project is to evaluate the efficacy of molecular and genetic modifiers in a degenerating retina. Her studies will greatly enhance understanding of genetic factors that influence severity of retinal disease, and provide potentially powerful targets for improved therapies to treat or prevent multiple forms of retinal disease.
Yuk Fai Leung, Ph.D.
Dept of Biological Sciences, Purdue University
Project: Research in gene regulatory networks in retina and RPE
There have been many research studies that have identified the underlying genetic causes of retinal degenerative diseases. However, without a fundamental understanding of the development of retina and retinal pigment epithelium (RPE), it would be difficult to elucidate the developmental mechanisms that are altered by these genes, not to mention designing effective treatments. Dr. Leung and his team are studying a novel irx7 (gene) regulatory network and its function in retinal development of zebra fish. Dr. Leung’s work will (1) elucidate the extent to which irx7 is regulating cellular differentiation in retina, and (2) clarify a framework of the irx7 regulatory network. This will greatly facilitate the investigation of molecular controls of normal zebra fish retinal development, which will in turn establish a strong scientific foundation for studying disease genes that cause retinal degeneration, and ultimately assist the design of better treatments for retinal degeneration.
Kristina Narfstom, D.V.M.
Dept of Veterinary Medicine, University of Missouri
Project: Research in large animal models of retinal degeneration with an emphasis on proof-of-concept
Summary: Dr. Narfstrom is investigating the implantation of light-sensing microchips in the retinas of animal models. The chips contain thousands of miniature solar cells that turn light into electrical current and early studies show that they may have even further benefits for people with RP in that they seem to actually slow progression of the disease. In addition, Dr. Narfstrom hopes to use gene replacement therapy to restore sight in the same animal model. Success with animal models would pave the way for using this approach in people with RP. Narfstrom already has had success using gene therapy to restore sight to French sheepdogs that suffer from another inherited retinal disorder. The dogs, called Briards, are born with night blindness and poor daylight vision that get progressively worse with age.
David Pepperberg, PhD
University of Illinois at Chicago
Project: Exploring the use of nanotechnology to restore vision to damaged retinal cells.
Photoreceptor degenerative diseases such as age-related macular degeneration (AMD) destroy the ability of rod and cone photoreceptors to respond to light and to transmit visual signals to “post-photoreceptor” nerve cells in the inner layers of the retina. However, the post-photoreceptor nerve cells themselves often appear to remain healthy in the diseased retina. As a possible therapy for AMD and related retinal diseases, Dr. Pepperberg and his colleagues are working to develop implantable, nanoscale molecular structures that can directly stimulate the post-photoreceptor nerve cells in response to light, and thus bypass the non-functioning photoreceptors. The immediate focus of their research is to develop prototypes of the desired molecular device, and to test the activities of these prototypes in two kinds of biological systems: (1) single, isolated cells that have been engineered to express a given type of postsynaptic receptor protein; and (2) retinal tissue obtained from animal models. We anticipate that this research will identify structures ultimately suitable for testing in human subjects.
Vladlen Slepak, Ph.D.
Bascom Palmer Eye Institute, University of Miami
Project: The role of light-dependent movement of transducin in retinal rods.
Summary: Bright light damages photoreceptor cells because the eye focuses reflected sunlight on the retina. It is also known that light can exacerbate retinal degeneration. The exact molecular mechanisms that protect photoreceptor cells and the reasons these protective mechanisms malfunction in disease are not completely understood. Several years ago scientists discovered that a crucial protein responsible for light reception, transducin, which in darkness localizes to the rod outer segments, and then re-localizes across the cell in bright light. Dr. Slepak’s research will uncover new information about photoreceptor cell biology that will allow us to understand how rod cells protect themselves from damaging levels of light. Specifically, this project will test the current hypothesis that the translocation of transducin to the inner compartments of rod cells has a cytoprotective function. Potentially, this research will identify novel proteins that influence cell survival, which can be targeted pharmacologically or through gene therapy.
Alexander Sumaroka, Ph.D.
Scheie Eye Institute, Univ of Pennsylvania
Project: Retinal Mapping For Targeting Treatment in Retinitis Pigmentosa
Summary: Inherited retinal degenerations in the family of diseases known as retinitis pigmentosa will be studied with optical coherence tomography, mainly to inquire about the integrity of the photoreceptor layer. Structural abnormalities of the inner retina, suggesting the process of retinal remodeling, will also be defined. The present work will use state-of the-art high-resolution instrumentation. Mapping of the photoreceptor layer has already been used in the University of Pennsylvania gene therapy clinical trial to target appropriate retinal regions for treatment and this approach has proven valuable.
Veena Theendakara, Ph.D.
Jules Stein Eye Institute, UCLA
Project: To perform research into novel cone photoreceptor gene and mechanisms of
ZBED4, a novel protein with mutations causing cone-rod dystrophy
Summary: Dr. Theendakara and her colleagues have recently identified ZBED4, a novel protein present in the nucleus and cytoplasm of cone photoreceptors. In addition, they found a mutation in the ZBED4 gene associated with disease in patients with cone-rod dystrophy. The objectives of their work are to investigate the movement of the ZBED4 protein between the nucleus and cytoplasm of cone photoreceptor cells; and to screen patients for mutations in the ZBED4 gene and establish genotype-phenotype correlations for early detection of disease and future intervention.