Midwest Eye-Banks is a not-for-profit organization dedicated to eye restoration through the recovery, evaluation and distribution of human eye tissue to people with blinding eye conditions. The organization also supports preliminary research for the causes and cures of blinding eye conditions. This year, six of the twelve research grants and two of the seven student stipends were awarded to Wayne State's School of Medicine, totaling nearly $100,000. Research topics included diabetic retinopathy, bacterial keratitis, and choroidal melanoma.
The purpose of these small grants is to provide the funding for pilot studies, which are valuable in determining whether a hypothesis has potential and should be further pursued. If a topic does merit continued investigation, these grants make it possible for researchers to apply for larger national and international research funds.
"Often times, it takes a small amount of seed money for the initial experiments," commented Dr. Joseph Dunbar, associate vice president for Research at Wayne State University. "Without the funding for these preliminary investigations, we would never get to the larger, more comprehensive studies that ultimately change people's lives. The portion of awards going to Wayne State faculty and students exemplifies the ingenuity of our researchers, who are looking at problems in new ways, and looking to improve treatments which, at present, are of a high cost to patients' quality of life."
Dr. Jayne S. Weiss, M.D., professor of Ophthalmology and Pathology and resident of Bloomfield, Mich., received $15,000 for her study concerning Schnyder Crystalline Corneal Dystrophy (SCCD), a rare inherited corneal disease predominant in people of Finnish or Swedish descent. Having studied SCCD for nearly two decades, Weiss has made tremendous headway in understanding the genetics of the disease, which causes gradual vision loss due to lipid accumulation that clouds the cornea. In 2007 she identified UBIAD1 as the abnormal gene that causes SCCD. She is now working to develop an animal model for the disease.
Dr. Keping Xu, assistant professor of Anatomy and Cell Biology, Ophthalmology, and a member of the Kresge Eye Institute, received two $15,000 awards, the first of which also deals with Schnyder Crystalline Corneal Dystrophy. Dr. Xu, a resident of Troy, Mich., will investigate if and how the abnormal gene identified by Weiss influences intracellular biochemistry or modifies other proteins regulating cholesterol transport and storage, thus resulting in the abnormal lipid accumulation seen in SCCD. Using cell lines of connective tissue in the cornea, Keping and her lab will be able to conduct extensive studies on the cellular and molecular biology of cell mutations, to reveal abnormal gene activities, and to understand the pathogenesis of SCCD. Ultimately, the study will give direction to identifying potential pharmacological methods to slow the progression of the disease.
Dr. Xu's second $15,000 grant will study a complication of diabetes that slows the healing rate of wounds to the outermost surface of the eye, called the corneal epithelium. This layer of the cornea acts as a barrier, protecting the eye from noxious environmental agents that may cause surface scrapes or incisions into the cornea. In the instance of a wound to the corneal epithelium, a key receptor known as the epidermal growth factor receptor, or EGFR, is activated to initiate the healing process. In diabetes patients, however, this self-repair function of the corneal epithelium is compromised. This occurs, Keping hypothesizes, due to hyperglycemia negatively affecting the signaling pathway of the EGFR. She plans to investigate how hyperglycemia has this effect, and will also determine if manipulation of the EGFR pathways in diabetic patients can accelerate epithelial wound healing to faster speeds. These efforts will be made with the ultimate goal to identify effective treatments for the delayed corneal epithelial wound healing in diabetic patients.
Dr. Xi Huang, assistant professor of Anatomy and Cell Biology and resident of Livonia, Mich., received a $15,000 grant to investigate the mechanisms underlying bacterial keratitis. One of the most common and destructive of bacterial diseases, especially in extended-wear contact lens users, keratitis induced by the bacterium Pseudomonas aeruginosa can cause rapid destruction of the cornea, sometimes within 24 to 48 hours. One of Huang's focuses is the proteins involved in the initial defense against P. aeruginosa and other invading pathogens, called Toll-like receptors (TLR). To learn more about what facilitates the infection into severe stages, he will conduct a study comparing the role of TLR cells in cases of successful immune resistance to cases of corneal perforation - the most severe complication of the bacterial infection resulting in inflammation and possible loss of an eye. Another focus is assessing a potential correlation between triggering receptors expressed in myeloid cells (TREMS), and immune response to P. aeruginosa keratitis.
Dr. Pukhrambam L. Singh, assistant professor of Anatomy and Cell Biology and resident of West Bloomfield, Mich., received $14,900 for research aimed at understanding, treating and preventing the progression of diabetes-related diseases of the eyes and kidneys. Singh is investigating a molecular defect called Epigenetic Chromatin Remodeling, the term used when cells continue to produce abnormal proteins or metabolic defects - processes characteristic of hyperglycemia - even after blood glucose levels are brought back to a normal level. This delayed response of cells returning to a normal state has been hypothesized as one of the reasons behind the development of vascular and microvascular diseases in people with diabetes. Singh hopes to pinpoint these molecular defects, which could result in pharmacological and gene therapy approaches to stopping or reversing progression into these diseases.
Dr. Rodney Braun, associate professor of Anatomy and Cell Biology and resident of Ferndale, Mich., received $15,000 for a new treatment for choroidal melanoma - a solid eye tumor arising from the pigmented cells of the choroid, which is the dense network of blood vessels at the back of the eye. The optimal treatment of this tumor is still under debate, despite its severe consequences - the mortality rate for this form of melanoma five years after diagnosis ranges from 35 to 90 percent, depending on the type and size of the tumor, and current therapy typically results in vision loss. Furthermore, if the tumor metastasizes to the liver, there are at present no effective therapies. By developing a model that more closely mimics the human disease, Dr. Braun's laboratory will be able to investigate the link between the primary tumor and the metastatic disease, which in turn be used to test new treatments for both stages of this type of melanoma.
In addition, two of the student stipends were awarded to Wayne State for projects on different aspects of some of the same ocular diseases. Zimei Zhou, a Ph.D. student in the Department of Anatomy and Cell Biology and resident of Detroit, Mich., received a $2,500 stipend for a project investigating apoptosis and neuropeptides in the progression of P. aeruginosa keratitis. Working in the laboratory of Dr. Linda Hazlett, chair of Anatomy and Cell Biology, Zhou is examining the pattern of apoptosis - or programmed cell death - in corneas infected with P. aeruginosa. Already shown to be an important factor in the progression of other infections, understanding the pattern of apoptosis in regards to P. aeruginosa keratitis could lead to the eventual control of the disease.
Dr. Sally Madsen-Bouterse, a post doctoral research associate in the Department of Ophthalmology and resident of Ferndale, Mich., received a $2,500 stipend for research that will investigate the development of diabetic retinopathy, a complication of diabetes that is the leading cause of blindness in young adults in the United States. Working in the lab of Dr. Renu Kowluru, professor of Ophthalmology, Madsen-Bouterse is interested in evaluating the role of the enzyme GAPDH as a mediator of hyperglycemia-induced apoptosis in capillary cells of the retina. The results of this work will bring a greater understanding to the hyperglycemia-induced mechanisms that contribute to the pathogenesis of diabetic retinopathy.
Wayne State University is one of the nation's pre-eminent public research universities in an urban setting. Through its multidisciplinary approach to research and education, and its ongoing collaboration with government, industry and other institutions, the university seeks to enhance economic growth and improve the quality of life in the city of Detroit, state of Michigan and throughout the world.