Jian-Xing Ma M.D. Ph.D.
Laureate Professor and Chairman
- Angiogenesis and inflammation in diabetic complications
- Vitamin A metabolism and retinal neurodegeneration
- M.D. Jiangxi Medical College, China
- M.S. Chinese Academy of Medical Sciences, Beijing, China
- Ph.D. Medical University of South Carolina, Charleston, SC
1. Vitamin A metabolism and retinal degeneration: Vitamin A is essential for vision. However, vitamin A is all-trans retinol which needs to be converted to 11-cis isoforms to be used for vision. Retinal isomerohydrolase is a key enzyme for generating 11-cis retinal, the chromophore for visual pigment, from vitamin A. My group is the first who showed direct evidence indicating that RPE65 is the isomerohydrolase. Further, we found that RPE65 is an iron-binding protein. The identification of the function of RPE65 opened a new era for the investigation of retinal dystrophies caused by RPE65 mutations in patients. Currently, we are studying the mechanism of this unique and important enzyme and investigating how mutations in this enzyme cause retinal degeneration.
2. Oxidative stress and inflammation in diabetic microvascular complications and age-related-macular degeneration (AMD): Diabetic retinopathy is a major microvascular complication of diabetes. AMD is a leading cause of blindness. Oxidative stress, inflammation and vascular dysfunctions such as vascular leakage are known to play important roles in these disorders. Currently, there is no satisfactory treatment, as their pathogenesis is uncertain. Recently, we have reported that the Wnt pathway activation is responsible, at least in part, for these microvascular complications in diabetic retinopathy and AMD. We are studying the mechanism for the Wnt pathway activation in these diseases. The goal of this research is to identify novel therapeutic targets for these diseases.
3. Endogenous angiogenic inhibitors, pathological angiogenesis, inflammation and vascular leakage in diabetes: Pathological angiogenesis (neovascularization), inflammation and vascular leakage are common features of diabetic vascular complications and other diseases such as age-related macular degeneration, cancer, infections and glaucoma. We have identified several peptide angiogenic inhibitors endogenously expressed in ocular and vascular tissues. We have shown that decreased levels of these inhibitors are associated with inflammation, fibrosis, vascular leakage and neovascularization in diabetic retina and kidney. Our recent experiments showed that these peptides inhibit inflammation in diabetic retina, protect blood-retinal barrier, reduce vascular leakage and inhibit retinal neovascularization in diabetic retinopathy animal models. Moreover, we have shown that these angiogenic inhibitors also inhibit inflammation and fibrosis in diabetic kidney and significantly reduce proteinuria in a diabetic rat model. We are using molecular biology and physiology methods to study the molecular mechanisms underlying the vascular activities of these peptides and their physiological functions. We will also explore the therapeutic potential of these peptides in diabetic complications. The long-term goal is to develop a new, non-invasive therapy using these natural peptides to block neovascularization and vascular leakage in diabetic complications.
- Park, K., Chen, Y., Hu, Y., Mayo, A.S., Kompella, U.B., Longeras, R. and Ma, J-x. (2009) Nanoparticle-mediated Expression of an Angiogenic Inhibitor Ameliorates Ischemia-induced Retinal Neovascularization and Diabetes-induced Retinal Vascular Leakage. Diabetes, 58, 1902-1913.
- Chen, Y., Hu, Y., Zhou, T., Zhou, K.K., Mott, R., Wu, M., Boulton, M., Lyons, T., Gao, G. and Ma, J-x. A New Pathogenic Mechanism for Diabetic Retinopathy. Am J Pathol. 175, 2676-2685.
- Takahashi, Y., Moiseyev, G., Ablonczy, Z., Chen, Y., Crouch, R.K., and Ma, J-x. (2009) Identification of a Novel Palmitylation Site Essential for Membrane Association and Isomerohydrolase Activity of RPE65. J. Biol. Chem. 284, 3211-3218.
- Zhang, S.X., Wang, J.J., Lu, K. Mott, R. and Ma, J-x. (2006) Therapeutic potential of angiostatin in diabetic nephropathy. J. Am. Soc. Nephrol., 17, 475-486.
- Moiseyev, G., Chen, Y., Takahashi, Y. and Ma, J-x. (2005) RPE65 is the isomerohydrolase in the visual cycle. Proc. Natl. Acad. Sci. USA, 102, 12413-12418.
- NIH R01EY012231: Studies of RPE65. Ma (PI)
- OCAST HR07-060: The pathogenesis of choroidal neovascularization. Ma (PI)
- NIH P20RR024215: Mentoring Diabetes Research in Oklahoma. Ma (PI)
- ADA 1-08-RA-115: A novel renoprotective factor in diabetic nephropathy. Ma (PI)
- NIH R01 EY019309: A novel pathogenic mechanism for diabetic retinopathy. Ma (PI)
- NIH R01 EY018659: The role of the wnt signaling pathway in choroidal neovascularization. Ma (PI)
- NIH P20 RR024215-03S: Mentoring diabetic research in Oklahoma (supplement). Ma (PI)
- NIH R01 EY019309-01S1: A new pathogenic mechanism for diabetic retinopathy (supplement). Ma (PI)
- NIH R01 DK80043: Lipoproteins and PEDF in the Vascular Complications of Diabetes. Lyons (PI)
Office telephone: (405) 271-4372