Retina Research Foundation Renewal Research Grants 2010

Baylor College of Medicine – Cullen Eye Center

Ramon L. Font, M.D. Cullen Eye Institute Baylor College of Medicine, Houston, TX Immunohistochemistry and Molecular Biology in Ophthalmic Pathology Our research interest is to study the pathogenesis and molecular diagnosis of the common fungi as well as the rare fungi.  We studies mycotic infections of the eye by molecular biology techniques in an effort to determine the accurate and prompt identification of the different fungal organisms.  The basic and clinical research studies will provide valuable insights in the pathogenesis and diagnosis of neoplastic lesions of the eye and ocular adnexa.

Samuel Miao-Sin Wu, Ph.D. Cullen Eye Center Baylor College of Medicine, Houston, TX Pharmacological and Genetic Mechanisms Underlying Retinal Cell Death in Glaucoma and Age-Related Macular Degeneration His lab developed one animal model for glaucoma and four mouse models for ARMD.  By using these models, this research Team identified 6 pharmacological agents that are protective against retinal cell damage in glaucoma and ARMD, including Brain-derived neurotrophic factor (BDNF).

Baylor College of Medicine - Other

Rui Chen, Ph Dept. of Mocular and Human Genetics Baylor College of Medicine, Houston, Texas Functional Analysis of Pour6 Genes in the Retina We plan to determine the LCA3 disease gene.  In addition, we will conduct mapping of additional novel LCA loci (aim 2).  Finally, we plan to generate conditional and nuli alleles of the mouse POU6f1 (aim3).  Specifically, we will generate targeting constructs, electroporate ES cells and identified targeted alleles, generate climatic mice carrying these alleles by blastocyst injection, and obtain germline transmission of these alleles.  We expect to be able to observe loss of function phenotypes near the end of the period.

Richard Hurwitz, M.D. Director, Texas Children's Hospital Retinoblastoma Center - Pediatrics, Ophatalmology and Molecular and Cellular Biology - Baylor College of Medicine, Houston, TX Immune Consequences of Gene Therapy for Ocular Disorders The laboratory studies the use of gene therapy approaches to treat ocular disease.  Retinoblastoma, the most common form of cancer of the eye in children is sometimes complicated by small pieces of cancer cells that break away from the main tumor and grow in the vitreous. These vitreous seeds are very difficult to treat.  The preliminary data has shown that gene therapy adenoviral vectors can be safely delivered to the eyes of children with retinoblastoma complicated by vitreous seeds. In addition, the vitreous tumor seeds were eradicated in these children.

Milan Jamrich, PhD Dept of Molecular and Cellular Biology Baylor College Of Medicine, Houston, Texas Function of TX in the Specification, Differentiation and Survival of Vertebrate Retinal Cells Our research is focusing on the role of the homeobox-containing gene Rx in the development, differentiation and survival of vertebrate retinal cells. We have shown previously that Rx has a critical role in the vertebrate eye formation.  Overexpression of Rx in frog embryos results in the development of giant eyes and the targeted elimination of Rx in mice results in a lack of eye formation. It was found by others that mutations in Rx genes cause lack of eye development in the zebrafish and medaka fish. Finally, mutations in human RX result in anophthalmia. Because it was shown that mutations in the human QRX, a gene very similar to Rx, are involved in retinal degeneration, we are currently investigating the role of Rx in the survival of retinal cells. Our preliminary data suggests that Rx has a critical role in the survival of retinal cells and the absence of its function causes retinal degeneration and detachment.

Graeme Mardon, Ph.D. Department of Pathology Baylor College of Medicine, Houston, TX Genetic and Molecular Analysis of Retinal Development This work focuses on two conserved genes (named Dach and senseless) that specify retinal cell fates during development. Both genes are necessary for normal retinal development in the fruit fly Drosophila melanogaster and are highly conserved in mammals, including humans.  One goal of our work has been to determine whether the mammalian Dach genes also play an essential role in eye development and the team is using gene targeting to this end.  A second goal of the project is to identify new, conserved genes that are also required for proper eye formation and we are using the power of Drosophila genetics to find genes that interact with senseless during retinal development.

University of Wisconsin-Madison

Curtis R. Brandt, Ph.D. Ophthalmology and Visual Science University of Wisconsin Medical School, Madison, WI Gene Therapy for Retinal Degenerative Diseases This laboratory is focusing on using Herpes simplex virus based vectors for ocular gene delivery.  Previously, we have shown that a therapeutic gene can be delivered to the retina with a positive effect in rodents.  We have also shown that genes can be delivered to the retina in primates but a transient inflammatory response is induced.  We are currently focusing our efforts on understanding why the vector induces inflammation in primates but not in rodents.  Understanding the mechanisms involved will allow us to develop strategies to block the effect.

Barbara E. Klein, MD, MPH Dept. of Ophthalmology and Visual University of Wisconsin Medical School, Madison, WI Associations of Retinal Microvascular Caliber in Pregnant Diabetic Women Retinal blood vessel diameters have been found to be associated with micro and macrovascular diseases and risk factors for them in persons with and without diabetes.  Retinal blood flow is increased in pregnant women perhaps as much as three times than in women who are not pregnant.  Whether this is accomplished by widened retinal blood vessels during pregnancy has not been assessed.  Pregnancy in diabetic women increases risk of proteinuria and high blood pressure above that already heightened risk of these problems in those with diabetes.  We hypothesize those changes in retinal blood vessel diameters during pregnancy are makers of heightened risk of development of these conditions.

Leonard A. Levin, MD, PhD Department of Ophthalmology & Visual Sciences University of Wisconsin Medical School, Madison, WI Pharmacological Protection of Endothelial Cells for  Retinal Vascular Disease Many blinding retinal diseases result from abnormalities of blood vessels. In some diseases, such as diabetic retinopathy or as the results of radiation, the initial event is damage to endothelial cells, the cells that line the inside of the blood vessels. We have previously demonstrated, in collaboration with ?Dr. Timothy Kern of Case Western Reserve University, that this endothelial cell death can be ameliorated in a transgenic mouse, and that diabetic retinopathy progresses less rapidly. However, it is impractical to use gene regulation of this type in patients. Instead, we have worked on developing novel drugs that block cell death. Recently, we discovered that some of these drugs, named borane-protected phosphines, block endothelial cell death in tissue cultures. We now propose to study their feasibility as treatments for retinal vascular disease.

University Of Texas

Louise C. Strong, M.D. Molecular Genetics University of Texas M.D. Anderson Cancer Center, Houston, TX Genetic Etiology of Retinoblastoma The goals of our research include understanding the roles of the tumor suppressor genes retinoblastoma gene (Rb1) and  p53 in the development of the ocular and non-ocular tumors that occur in hereditary retinoblastoma patients.  We have  focused specifically on characterizing unusual retinoblastoma patients.  We have focused specifically on characterizing unusual retinoblastoma gene mutations that have low penetrance (fewer tumors, older onset) on one hand, and on characterizing the Rb1 inherited mutations and p53 non-hereditary somatic mutations in non-ocular tumors (primarily sarcomas)arising in hereditary retinoblastoma patients.

Texas A & M University System Health Science Center/Scott & White Mem. Hospital

Lih Kuo, PhD Department of Systems Biology and Translational Medicine. Temple, Texas Effect for C-Reactive Protein and Statins on Retinal Arteriolar Function Recent studies have implicated that elevation of inflammatory marker C-reactive protein (CRP) is a major independent risk factor for vascular disorder during the development of cardiovascular disease including diabetes.  In the present application, we will test the hypothesis that elevation of intravascular level of CRP can lead to endothelial dysfunction and impair vasodilation by reducing NO bioavailability through enhanced oxidative stress.  We also hypothesize that administration of statins can improve CRP-impaired retinal endothelial function and vasodilation by enhancing endothelial NO production and reducing oxidative stress.