The investigator describes several lines of evidence in favor of the hypothesis that retinal glia when subjected to hypoxic injury release VEGF and TGF-beta and promote the breakdown of the blood retinal barrier in slightly different ways. The applicant presents the hypothesis that TGF-beta stimulates VEGF release and VEGF has an NO-mediated effect to increase transcytotic permeability. TGF-beta, in contrast, is proposed to increase paracellular permeability by matrix metalloproteinase (MMP)-mediated breakdown of the intercellular extracellular matrix (ECM).
The first aim of the study is to test the hypothesis that VEGF stimulates increased endothelial cell permeability by promoting transcytotic transport mediated by caveolae and nitric oxide (NO) signaling mechanisms.
The second aim will test the hypothesis that TGF-beta stimulates increased endothelial cell permeability by mechanisms involving either the MMP gelatinase or VEGF.
The third aim will test the idea that hypoxia induces endothelial cell hyperpermeability by promoting glial release of TGF-beta or VEGF. These studies will largely be carried out with cultured bovine endothelial cells. Since permeability increases promote tissue damage in various retinal diseases (e.g., ischemia, retinopathy of prematurity), it is important to understand the process leading to such increases so as to develop means for controlling it.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
Project #
Application #
Study Section
Visual Sciences C Study Section (VISC)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Medical College of Georgia (MCG)
Schools of Medicine
United States
Zip Code
Caldwell, Ruth B; Toque, Haroldo A; Narayanan, S Priya et al. (2015) Arginase: an old enzyme with new tricks. Trends Pharmacol Sci 36:395-405
Patel, Chintan; Narayanan, S Priya; Zhang, Wenbo et al. (2014) Activation of the endothelin system mediates pathological angiogenesis during ischemic retinopathy. Am J Pathol 184:3040-51
Jittiporn, Kanjana; Suwanpradid, Jutamas; Patel, Chintan et al. (2014) Anti-angiogenic actions of the mangosteen polyphenolic xanthone derivative ?-mangostin. Microvasc Res 93:72-9
Rojas, Modesto; Zhang, Wenbo; Xu, Zhimin et al. (2013) Requirement of NOX2 expression in both retina and bone marrow for diabetes-induced retinal vascular injury. PLoS One 8:e84357
Elms, S C; Toque, H A; Rojas, M et al. (2013) The role of arginase I in diabetes-induced retinal vascular dysfunction in mouse and rat models of diabetes. Diabetologia 56:654-62
Patel, Chintan; Rojas, Modesto; Narayanan, S Priya et al. (2013) Arginase as a mediator of diabetic retinopathy. Front Immunol 4:173
Liu, Hua; Zhang, Wenbo; Xu, Zhimin et al. (2013) Hyperoxia causes regression of vitreous neovascularization by downregulating VEGF/VEGFR2 pathway. Invest Ophthalmol Vis Sci 54:918-31
Narayanan, S Priya; Rojas, Modesto; Suwanpradid, Jutamas et al. (2013) Arginase in retinopathy. Prog Retin Eye Res 36:260-80
El-Remessy, Azza B; Franklin, Telina; Ghaley, Nagla et al. (2013) Diabetes-induced superoxide anion and breakdown of the blood-retinal barrier: role of the VEGF/uPAR pathway. PLoS One 8:e71868
Alkilany, Alaaldin M; Shatanawi, Alia; Kurtz, Timothy et al. (2012) Toxicity and cellular uptake of gold nanorods in vascular endothelium and smooth muscles of isolated rat blood vessel: importance of surface modification. Small 8:1270-8

Showing the most recent 10 out of 86 publications