Jacque Duncan, M.D.
Beckman Vision Center, University of California - San Francisco
Project: High resolution retinal imaging in patients with retinal degenerations
Summary: Dr. Duncan and her team will correlate the images of retinal structure produced by the Adaptive Optics Scanning Laser Ophthalmoscope (AOSLO) with standard measures of retinal structure created with an instrument known as Optical Coherence Tomography (OCT). OCT images provide information about retinal structure in cross-section, while AOSLO gives en face images of individual cones. By combining these two techniques Dr. Duncan hopes to learn more about how changes in cone structure relate to vision loss in patients with retinal degenerations. In addition, Dr. Duncan will correlate the images of cone structure obtained using AOSLO with standard clinical measures of retinal function used in Ophthalmology clinics, including visual acuity, automated perimetry, fundus photography including fundus autofluorescence and multifocal electroretinography (mfERG), to learn how well the cones work or are able to see.
Gustavo Aguirre, D.V.M., Ph.D.
Dept of Genetics, School of Veterinary Medicine, University of Pennsylvania
Project: Developing Retinal Therapies in Models of Retinal Degeneration
Proof of principle studies in retinal disease models have demonstrated that experimental therapies can be evaluated and transitioned into clinical trials for retinal diseases in human patients (e.g., gene therapy for LCA; CNTF via encapsulated cell based therapy technology). Dr. Aguirre will continue to use disease relevant models to develop or evaluate novel therapies that have the potential for restoring sight or preventing/slowing down the loss of vision in human patients.
Muayyad Al-Ubaidi, Ph.D.
Dept of Cell Biology, University of Oklahoma
Project: To evaluate pharmacological and neurotrophic agents to rescue photoreceptor cells in RP animal models.
Summary: Since a greater proportion of retinal degenerative diseases are still of unknown causes, there exist the need to further study other aspects of normal retinal function. Furthermore, in most cases where the mutation is known, it is not known how that mutation has altered the function of the protein leading to the degenerative disease phenotype. Dr. Al-Ubaidi and his team chose to understand how modulations in a post-translational modification can alter retinal function. The gained knowledge will help them understand how a protein functions and therefore, how a mutation would alter that function leading to a blinding disease. They will identify all sulfated retinal proteins and will choose those that have been involved in retinal disease for further study. They will then study how lack of sulfation altered that function. This will allow them to develop strategies, gene based or pharmacological, to counter the effects of the mutation.
Tomas Aleman, M.D.
Scheie Eye Institute, University of Pennsylvania
Project: Retinitis Pigmentosa: Paving the Path to Treatments Through Detailed Understanding of Disease Expression
Summary: Success of ongoing gene therapy trials for Leber Congenital Amaurosis has raised expectations that other forms of inherited retinal degeneration may also be treatable. Detailed characterizations of patients, part of the groundwork that was necessary to initiate these trials, will be performed in other inherited retinal degenerative disorders to increase understanding of human disease expression and mechanism. The knowledge gained will be used to ask specific questions relevant for the planning of future treatment trials for these conditions.
Jonathan Ash, Ph.D.
Dept of Ophthalmology, University of Oklahoma
Project: To perform research on neuroprotection that would be relevant to genetic photoreceptor degenerations
Summary: In most cases of retinal degeneration, photoreceptor death is the result of long-term inflammation, exposure to environmental insults, and genetics. While disease causing genes are present before birth, patients with retinitis pigmentosa or age related macular degeneration typically do not develop disease for 50 to 80 years. The protracted time to develop symptoms suggests that retinal neurons have an endogenous mechanism for protection from chronic injury. The main focus of Dr. Ash’s work is to identify the mechanism of stress-induced endogenous protection of photoreceptors, and once identified, he and his team will develop these protective mechanisms into new therapeutics, with the goal of delaying or preventing blindness resulting from inherited retinal degenerations.
Joseph Carroll, Ph.D.
Eye Institute, Medical College of Wisconsin
Project: Advanced Retinal Imaging and Improving the Success of Gene Therapy
Summary: Dr. Carroll and his team will use adaptive optics, allowing them to see individual photoreceptor cells in the retina, and optical coherence tomography, allowing them to see the layers of the retina. This information will be combined with genetic data and clinical data on each patient to develop a high-resolution genotype-phenotype correlation that carries with it significant predictive power with regard to treating this and other retinal degenerations.
Arlene Drack, M.D.
University of Iowa Hospitals and Clinics
Project: To perform clinically-relevant molecular genetics research in syndromic and non-syndromic RP
Summary: Dr. Drack’s research is focused on treatment strategies for mouse models of human retinitis pigmentosa and Bardet Biedl syndrome (BBS). Dr. Drack’s group was the first to demonstrate genetic heterogeneity of BBS by identifying linkage to three different chromosomal locations in three large consanguineous tribes of Bedouin Arabs from Israel. Furthermore, her laboratory has independently identified seven of the twelve known BBS genes and recently developed knockout mouse models of many of those genes. In the next few years, Dr. Drack and her team intend to develop and test viral-mediated gene replacement therapy in mouse models of these diseases; and clinically and molecularly characterize a large number of patients affected with BBS to establish the natural history of the vision loss in this disease as well as to identify a large number of individuals who could be invited to participate in a future human clinical trials of gene therapy for these diseases.
Erica Farber, Ph.D.
Jules Stein Eye Institute, University of California – Los Angeles
Project Title: Characterization of microRNAs in stem cell microvesicles
Summary: Fish and amphibians retain stem cells with the ability to regenerate the retina after injury. However, mammals have lost this ability. Recently, dormant stem cells were discovered in the mammalian eye. Further elucidation of the communication role of microvesicles within stem cell niches may reveal ways for microvesicles to awaken these dormant stem cells and lead to retina repair. Additionally, microvesicles released from cells engineered to express mRNA, proteins, or siRNA may be useful to deliver these small molecules to the eye. Dr. Farber and her collegues will characterize the micro RNAs in stem cell microvesicles and establish a way to use microvesicles as vehicles for the transfer of specific small molecules to retinas affected by degenerative disease.
Jeffrey Goldberg, M.D., Ph.D.
Bascom Palmer Eye Institute, University of Miami
Project: Research leading to the development of therapeutic tools for photoreceptor diseases
Summary: Retinal degenerations such as retinitis pigmentosa often end with the death of retinal neurons such as rod and cone photoreceptors. Although it may be possible to salvage these cells before they die, for the many patients who have lost these cells, we must figure out a way to replace them. Little is known about how to harvest retinal stem cells, how to direct them to the proper location in the retina, how to push them to differentiate into photoreceptors, and how to integrate them into the retina. Dr. Goldberg and his team are now attempting to address retinal degenerative disease by combining cell culture and nanotechnology to provide novel approaches to stem cell and cell replacement therapy. Dr. Goldberg’s hope with these experiments is to enhance the efficacy of stem cell and photoreceptor transplantation and integration into the retina, and thereby bring back vision in retinal degenerative diseases.
Michael Grassi, MD
University of Chicago
Project: Collaborative effort to facilitate the discovery and testing of effective compounds to treat retinal degenerative disease.
Summary: Dr. Grassi has developed a multidisciplinary, inter-institutional collaboration between basic scientists and clinicians in Chicago to investigate the mechanisms that may result in apoptotic photoreceptor death in RP. Using a cellular model of RP, the research team will screen hundreds of thousands of small molecules to identify those compounds and genes that retard or prevent apoptosis. In addition, the cell culture system will enable a genome scale screen using RNA interference to assess the role of over 25,000 individual genetic perturbations in photoreceptor cell survival. Results from the screenings will be extended to animal models, which will enable the development and introduction of new therapies to better treat, and perhaps even prevent RP.