Jian-xing Ma, MD, PhD
Laureate Professor &
Chairman, Department of Physiology
Dr. Ma's Research Group
941 Stanton L. Young Blvd., BSEB 328B
Oklahoma City, OK 73104-5020
- Pathogenesis of neurodegeneration and neuroprotective genes in the retina: The retina consists of neurons which convert light energy into neuronal signals. The normal function of these photoreceptor cells is essential for the vision. Photoreceptor degeneration has been found in many blinding diseases. Using gene knockout animal models and molecular biology approaches such as microarray, proteomics, yeast-two-hybrid system and gene delivery, we are identifying genes responsible for the photoreceptor degeneration and the neuroprotective genes. We are also studying the roles of these genes in the retinal degeneration and exploring their potential applications in the treatment of retinal degeneration.
- Pathological angiogenesis, inflammation and vascular leakage in diabetes: Pathological angiogenesis in the retina (neovascularization), inflammation and vascular leakage (hyper-permeability) are common features of diabetic complications and many other diseases such as age-related macular degeneration, cancer, infections and glaucoma. Currently, there is no satisfactory treatment to block the neovascularization and vascular leakage, as their pathogenesis is uncertain. Recently, we have identified several peptide angiogenic inhibitors endogenously expressed in ocular tissues and found that decreased levels of these inhibitors are responsible for the neovascularization and vascular leakage. Using genetic engineering methods, we have expressed these inhibitors and showed that these recombinant peptides can stop neovascularization. They also protect blood-retinal barrier and reduce vascular leakage. We are using molecular biology, biochemistry methods and animal models to study the molecular mechanisms underlying the vascular activities of these peptides. The goal of this research is to develop a new, non-invasive therapy using these natural peptides to block neovascularization and vascular leakage in cancer and diabetes.
||PhD - Biochemistry, Medical University of South Carolina, Charleston
||MS - Pharmacology, Chinese Academy of Medical Sciences, Beijing, China
||MD - Jiangxi Medical College, China
Zhang B, Abreu JG, Zhou KK, Chen Y, Hu Y, Zhou T, He X, and Ma J-x. (2010). Blocking the Wnt Pathway, a Unifying Mechanism for an Angiogenic Inhibitor in the Serine Proteinase Inhibitor Family. Proc. Natl. Acad. Sci. USA. 107, 6900-6905.
Zhang B, Zhou KK, and Ma J-x. (2010). Inhibition of CTGF Over-expression in Diabetic Retinopathy by SERPINA3K via Blocking the WNT/Beta-catenin Pathway. Diabetes, in press.
Moiseyev G, Nikolaeva O, Chen Y, Farjo K, Takahashi Y, and Ma J-x. (2010). Inhibition of the visual cycle by A2E through direct interaction with RPE65 and implications in Stargardt's disease. Proc. Natl. Acad. Sci. USA., in press.
Zhou T, Zhou KK, Lee K, Gao G, Lyons TJ, Kowluru R, and Ma J-x. (2010) The Role of Lipid Peroxidation Products and Oxidative Stress in Activation of the Canonical Wnt Pathway in Diabetic Retinopathy. Diabetologia, in press.
Zhou T, Hu Y, Chen Y, Zhou K, Zhang B, Gao G, and Ma J-x. (2010). The pathogenic role of the canonical Wnt pathway in age-related macular degeneration. Invest. Ophthalmol. Vis. Sci., in press.
Nikolava O, Takahashi Y, Moiseyev G, and Ma J-x. (2010). Negative charge of the glutamic acid 417 residue is crucial for isomerohydrolase activity of RPE65. Biochem. Biophys. Res. Comm. In press.
Wang M, Wang JJ, Li J, Park K, Qian X, Ma J-x, and Zhang SX. (2009). Pigment Epithelium-derived factor (PEDF) suppresses adipogenesis via inhibition of the MAPK/ERK pathway in 3T3-L1 preadipocytes. Am. J. Physiol., 297, E1378-1387.
Muniz A, Betts BS, Trevino AR, Buddavarapu KC, Roman R, Ma J-x, and Tsin AT. (2009). Evidence for Two Retinoid Cycles in the Cone-Dominated Chicken Eye. Biochemistry. 48, 6854-6863.
Bai Y, Ma J-x, Zhu M, Zheng L, Ferrara N, and Le Y-z. (2009). Müller cell-derived VEGF is a significant contributor to retinal neovascularization. J. Pathol. 219, 446-454.
Farjo KM, Moiseyev G, Takahashi Y, Crouch RK, and Ma, J-x (2009). RDH10 has 11-cis-Retinol Dehydrogenase Activity and Interacts with Visual Cycle Proteins. Invest. Ophthalmol. Vis. Sci., 50, 5089-5097.
Park K, Chen Y, Hu Y, Mayo AS, Kompella UB, 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.
Nikolaeva O, Takahashi Y, Moiseyev G, and Ma J-x. (2009). Purified RPE65 shows isomerohydrolase activity after re-association with a phospholipid membrane. FEBS J, 276, 3020-3030.
Li J, Wang JJ, Chen D, Mott R, Yu Q, Ma J-x, and Zhang SX. (2009). Systemic Administration of HMG CoA Reductase Inhibitor Protects the Blood-retinal Barrier and Ameliorates Retinal Inflammation in Type 2 diabetes. Exp. Eye Res. 89, 71-78.
Chen Y, Hu Y, Zhou T, Zhou KK, Mott R, Wu M, Boulton M, Lyons T, Gao G, and Ma J-x.(2009). A New Pathogenic Mechanism for Diabetic Retinopathy. Am J Pathol. 175, 2676-2685.
Zhang B, Hu Y, and Ma J-x. (2009). SERPINA3K is an Endogenous Anti-inflammatory and Anti-oxidant Factor in the Retina. Invest. Ophthalmol. Vis. Sci., 50, 3943-3952.
Takahashi Y, Moiseyev G, Ablonczy Z, Chen Y, Crouch RK, 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.
Takahashi Y, Moiseyev G, Farjo K, and Ma J-x. (2009) Characterization of Key Residues and Membrane Association Domains in RDH10. Biochem. J. 419, 113-122.
Chen Y, Hu Y, Moiseyev G, Zhou K, Chen D, and Ma J-x. (2009) Photoreceptor Degeneration and Retinal Inflammation Induced by Very Low-density Lipoprotein Receptor Deficiency. Microvasc. Res. 78, 119-127.
Yu Y, Jenkins AJ, Nankervis AJ, Hanssen K, Scholz H, Henriksen T, Lorentzen B, Garg SK, Menard MK, Hammad SM, Scardo JC, Stanley JR, Dashti A, May K, Lu K, Aston CE, Zhang SX, Ma J-x, and Lyons TJ. (2008) Antiangiogenic factors and the prediction of pre-eclampsia in Type 1 diabetes. Diabetologia, 52, 160-168.
Qin C, Ghorbani ML, Wu M, Farbar JP, Ma J-x, and Foreman RD. (2008) Characterization of upper thoracic spinal neurons responding to esophageal distension in diabetic rats. Auton. Neurosci., 145, 27-34.
Yang Z, Mao X, Gong Q, Pan Q, Yang X, Cai W, Li C, Ma J-x, He Y, and Gao G. (2008) Critical effect of VEGF in the process of endothelial cell apoptosis induced by high glucose. Apoptosis, 13, 1331-1343.
Zhang B, and Ma J-x. (2008) SERPINA3K Prevents Oxidative Stress Induced Necrotic Cell Death by Inhibiting Calcium Overload. PlosOne. 3, e4077.
Vidro EK, Gee S, Unda R, Ma J-x, and Tsin A. (2008) Glucose and TGFβ2 Modulate the Viability of Cultured Human Retinal Pericytes and Their VEGF Release. Curr. Eye Res. 33, 984-993.
Zhang SX, Wang JJ, Dashiti A, Wilson K, Zou M-H, Szweda L, Ma J-x, and Lyons TJ. (2008). Pigment Epithelium-derived Factor (PEDF) mitigates inflammation and oxidative stress in retinal pericytes exposed to oxidized-LDL. J Mol Endocrinol, 41,135-143.
Wu M, Chen Y, Yu Y, Boulton ME, Ma J-x, Lyons TJ. (2008). Intra-retinal leakage and oxidation of LDL in diabetic retinopathy. Invest Ophthalmol Vis Sci 49, 2679-2685.
Wang J, Zhang SX, Mott R, Chen Y, Knapp RR, Cao W, and Ma J-x. (2008). Anti-inflammatory Effects of Pigment Epithelium-derived Factor in Diabetic Nephropathy. Am. J. Physiol. Renal Physiol. 294, F1166-1173.
Jenkins A, Zhang SX, Gosmanova A, Aston C, Dashti A, Baker MZ, Lyons T, and Ma J-x. (2008). Increased serum pigment epithelium derived factor levels in Type 2 diabetes patients. Diabetes Research and Clinical Practice 35, e5-e7.
Maguire AM, Simonelli F, Pierce EA, Pugh EN Jr, Mingozzi F, Bennicelli J, Banfi S, Marshall KA, Testa F, Surace EM, Rossi S, Lyubarsky A, Arruda VR, Konkle B, Stone E, Sun J, Jacobs J, Dell'osso L, Hertle R, Ma JX, Redmond TM, Zhu X, Hauck B, Zelenaia O, Shindler KS, Maguire MG, Wright JF, Volpe NJ, McDonnell JW, Auricchio A, High KA, Bennett J. (2008) Safety and Efficacy of Gene Transfer for Leber's Congenital Amaurosis. New Engl. J. Med. 358, 2240-2248.
Moiseyev M, Takahashi Y, Chen Y, Kim S, and Ma J-x. (2008). RPE65 from cone dominant chicken is a more efficient isomerohydrolase, compared to that from rod dominant species. J. Biol. Chem. 283:8110-8117.
Kanan Y, Kasus-Jacobi A, Moiseyev G, Sawyer K, Ma J-x, and Al-Ubaidi MR. (2008). Retinoid processing in core and Muller cell lines. Exp. Eye Res. 86:344-354.
Chen Y, Znoiko S, DeGrip WJ, Crouch RK, and Ma J-x. (2008). Salamander blue-sensitive cones lost during metamorphosis. Photochem. Photobiol. 84, 855-862.
Chen Y, Hu Y, Lu K, Flannery JG, and Ma J-x. (2007). VLDL Receptor, a Negative Regulator of the Wnt Signaling Pathway and Choroidal Neovascularization. J. Biol. Chem. 282:34420-34428.
Graham S, Ding M, Sours-Brothers S, Yorio T, Ma J-x, and Ma R. (2007). Downregulation of TRPC6 protein expression by high glucose, a possible mechanism for the impaired Ca2+ signaling in glomerular mesangial cells in diabetes. Am. J. Physiol. Renal Physiol. 293:F1381-1390.
Jenkins AJ, Zhang SX, Rowley KG, Karschimkus CS, Nelson CL, Chung JS, O’Neal DN, Januszewski AS, Croft KD, Mori TA, Dragicevic G, Harper CA, Best JD, Lyons TJ, and Ma J-x. (2007). Increased serum pigment epithelium derived factor is associated with microvascular complications, vascular stiffness, and inflammation in type 1 diabetes. Diabetes Med. 24:1345-1351.
Rajala A, Anderson RE, Ma J-x, Lem J, Al-Ubaidi MR, and Rajala RVS. (2007). G-Protein Coupled Receptor Rhodopsin Regulates the Phosphorylation of Retinal Insulin Receptor. J. Biol. Chem. 282:9865-9873.
Lu K, Zhou Y, Kaufman K, Mott R, and Ma J-x. (2007). Rat Strain-dependent Susceptibility to Ischemia-induced Retinopathy through Factors Regulating Retinal VEGF Expression. J. Mol. Endocrinol. 38:423-432.
Sandell LL, Sanderson BW, Moiseyev G, Johnson T, Mushegian T, Young K, Jean-Phillipe Rey J-P, Ma J-x, Staehling-Hampton K, and Trainor PA. (2007). RDH10 critically regulates tissue specific embryonic retinoic acid synthesis and is required for craniofacial, limb and organ development. Genes and Dev. 21:1113-1124.
Szatmari I, Pap A, Ruechl R, Ma J-x, Illarionov PA, Besra GS, Rajnavolgyi E, and Nagy L. (2006). PPARr controls CD1d expression by turning on retinoic acid synthesis in developing human dendritic cells. J. Exp. Med., 203:2351-2362.
Chen Y, Moiseyev G, Takahashi Y, and Ma J-x. (2006). Impacts of Two Point Mutations of RPE65 from Leber’s Congenital Amaurosis on the Stability, Subcellular Localization and Isomerohydrolase Activity of RPE65. FEBS Lett.. 580:4200-4204.
Takahashi Y, Moiseyev G, Chen Y, and Ma J-x. (2006). The roles of three palmitoylation sites of RPE65 in its membrane association and isomerohydrolase activity. Invest. Ophthalmol. Vis. Sci. 47:5191-5198.
Isayama T, Chen Y, Kono M, DeGrip WJ, Ma J-x, Crouch RK, and Makino CL. (2006). Differences in the pharmacological activation of visual opsins. Vis. Neurosci., 23:899-905.
Wu BX, Darden AG, Laser M, Crosson CE, Hazard ES, and Ma J-x. (2006). The Rat Apg3p/Aut1p Homologue is Up-regulated by Ischemic Preconditioning in the Retina. Mol. Vis. 12:1292-1302.
Kanan Y, Moiseyev G, Agarwal N, Ma J-x, and Al-Ubaidi MR. (2006). Light induction of multiple caspases and cell death in a cone photoreceptor cell line. Invest. Ophthalmol. Vis. Sci, 48:40-51.
Zhang SX, Wang JJ, Lu K, Mott R, Ma J-X. (2006). Therapeutic Potential Of Angiostatin In Diabetic Nephropathy. J. Am. Soc. Nephrol. 17:475-486.
Zhang SX, Wang JJ, Gao G, Shao C, Mott R, Longeras R, and Ma J-X. (2006). Pigment Epithelium-derived Factor (PEDF) Is An Endogenous Anti-inflammatory Factor. FASEB J. 20:323-325.
Zhang SX, Wang JJ, Gao G, Park K, and Ma J-x. (2006). Reciprocal regulation between pigment epithelium-derived factor (PEDF) and vascular endothelial growth factor (VEGF). Mol. Endocrinol. 37:1-12.
Wang JJ, Zhang SX, Mott R, Knapp R, Cao W, Lau K, and Ma J-x. (2006). Salutary effect of pigment epithelium-derived factor in diabetic nephropathy: evidence for anti-fibrogenic activities. Diabetes, 55:1678-1685.
Yang X, Chen R, Li C, Cai W, Ma J-X, Liu Q, Yang Z, Song Z, Liu Z, Gao G. (2006).Kringle 5 Of Human Plasminogen Suppresses Hepatocellular Carcinoma Growth Both In Grafted Xenografted Mice By Anti-angiogenic Activity. Cancer Biol. Ther. 5:399-405.
Yokota T, Kawakami Y, Nagai Y, Ma J-X, Tsai J-Y, Kincade KW, Sato S. (2006). Bone Marrow Lacks A Transplantable Progenitor For Smooth Muscle Type Alpha-actin Expressing Cells. Stem Cells, 24, 13-22.
Tomasek JJ, Haaksma CJ, Schwartz RJ, Vuong DT, Zhang SX, Ash JD, Ma J-X, Al-Ubaidi MR. (2006). Deletion Of Smooth Muscle α-actin Alters Blood-retina Barrier Permeability and Retinal Function. Invest. Ophthalmol. Vis. Sci. 47:2693-700.
Takahashi Y, Chen Y, Moiseyev G, and Ma J-X. (2006). Two Point Mutations Of RPE65 From Patients With Retinal Dystrophies Decrease The Protein Stability and Abolish The Isomerohydrolase Activity Of RPE65. J. Biol. Chem. 281:21820-825.
Murata M, Takanami T, Shimizu S, Kubota Y, Horiuchi S, Ma J-X, and Sato S. (2006). Inhibition Of Ocular Angiogenesis By Diced Small Interfering RNAs (siRNAs) Specific To Vascular Endothelial Growth Factor (VEGF). Curr. Eye Res. 31:171-180.
Moiseyev G, Takahashi Y, Chen Y, Gentleman S, Redmond TM, Crouch RK, and Ma J-X. (2006). RPE65 is an Iron(II)-dependent Isomerohydrolase in the Retinoid Visual Cycle. J. Biol. Chem 281:2835-3840.
Chen Y, Moiseyev G, Takahashi Y, and Ma J-X. (2006). RPE65 gene delivery restores isomerohydrolase activity and prevents early cone loss in Rpe65-/- mice. Invest. Ophthalmol. Vis. Sci. 47:1177-84.
Reviews and Invited Papers
Zhang SX, and Ma J-X. Ocular Neovascularization: Implication of Endogenous Angiogenic Inhibitors and Potential Therapy. Prog Retin Eye Res, Submitted (Invited review article).
Books Chapters and Manuscripts
Ma J-X, and Zhang SX. Endogenous Angiogenic Inhibitors in Diabetic Retinopathy. in "Ocular Angiogenesis: Diseases, Mechanisms and Therapeutics" Eds J. Tombran-Tink and C.J. Barnstable, Humana Press, Totowa, NJ. 2006, pp 23-44.