Understanding the basic molecular mechanisms of abnormal retinal neovascularization and vision loss with a special focus on Tissue Inhibitors of Metalloproteinases (TIMPs). Examination of the physiological and pathological pathways that regulate the developmentand maintenance of teh blood retinal barrier.
Research and Innovations:
With the discovery of TIMP-3 mutations being causative in an inherited retinal degeneration, Sorsby Fundus Dystrophy, in which patients developed florid choroidal neovascularization, we focused our studies on using the retina as a model to study the role of extracellular matrix and TIMPs in angiogenesis.
We have made significant progress in being able to dissect out the mechanisms by which mutations in TIMP-3 cause the Sorsby fundus dystrophy phenotype as well as identifying the regions of TIMP-3 that are responsible for angiogenesis inhibition. We have recently been awarded a patent for the use of TIMP-3 peptides for the inhibition of angiogenesis in a number of diseases in which neovascularization plays a major role. For the most part we have focused our efforts on the regulation of neovascularization in the eye with some activities in tumor angiogenesis.
Using both human, animal in vivo and in vitro studies we have identified insulin and betacellulin to play a role in the breakdown of the blood retinal barrier and likely be involved in the development of macular edema in patients with diabetes. We have established a novel transgenic zebrafish model that can be used for high throughput screening of drugs that effect retinal and brain vascular leakage. Our ultimate goal is the understanding, prevention and/or reversal of angiogenesis and macular edema, in an effort to control the devastating blinding consequences of ocular diseases.
Jian Hua Qi Ph.D.
Qi, JH, Ebrahem, Q, Moore, N, Murphy, G, Claesson-Welsh, L, Bond, M, Baker, A and Anand-Apte, B. (2003) Nature Medicine 9:407-415
Qi J, Dai G, Luthert P, Hollyfield J, Weber B, Heidi Stoehr and Anand-Apte B (2009) Upregulation of VEGF Receptor-2 in Endothelial Cells Expressing S156C-TIMP-3 Mutation Mediates Enhanced Angiogenesis: Implications for Choroidal Neovascularization in Sorsby Fundus Dystrophy. Journal of Biological Chemistry 284:19927-19936
Ebrahem Q, Vasanji A, Qi J, Klenotic P, Cutler A and Anand-Apte B (2010) Cross-talk between Vascular Endothelial Growth Factor (VEGF) and Matrix Metalloproteinases (MMPs) in the induction of Neovascularization In Vivo. American Journal of Pathology 176(1):496-503.
Xie, J., Farage, E., Sugimoto,M and Anand-Apte,B. (2009) BMC Dev Biol. 2010 Jul 23;10:76
Sugimoto, M, Cutler, A., Shen, B., Moss, SE., Iyengar, SK., Klein, R., Folkman, J and Anand-Apte, B (2013) Inhibition of EGF Signaling Protects the Diabetic retina From Insulin-Induced Vascular Leakage. Am J Pathol 183(3):987-995
Bell, B, Xie, J, Yuan,A, Kaul,C, Hollyfield, JG and Anand-Apte, B (2014) Retinal Vasculature Imaging in Adult Zebrafish In Vivo using Confocal Scanning Laser Ophthalmoscopy. Experimental Eye Research 129;107-118
Qi, J and Anand-Apte, B (2014) Tissue Inhibitor of Metalloproteinase-3 (TIMP3) Promotes Endothelial Apoptosis by a Caspase-Independent Mechanism. Apoptosis 2015:20(4):523-534