The PI hypothesis is that the cells of the aqueous outflow pathway can modulate aqueous humor outflow resistance through changes in cell shape, contraction and attachment; that the cytoskeleton in outflow pathway cells (both the inner wall of Schlemm's canal (SC) and the juxtacanalicular (JCT) cells) is involved in these cellular events; that in response to increases in intraocular pressure (IOP) the outflow pathway tissue distends and stretches both the cells in the JCT and inner wall of SC; that the resulting changes in cellular tension produce reorganization of cytoskeletal proteins that may be different in the two cell types, that then through induced changes in cell shape and attachment alter the dimension or direction of the flow pathway through the JCT and inner wall of SC, which allows a compensatory increase in fluid outflow. The PI hypothesizes that overexpression of constitutively active rho and/or alteration of myosin light chain phosphorylation will mimic the cytoskeletal (and cell shape and attachment) effects that occur with increased flow and/or stretching, and that their underexpression will interfere with these responses as well as that to certain (but not all) cytoskeletal drugs such as ethacrynic acid (ECA), ticrynafen and vinblastine.
The Specific Aims i nclude: 1)To characterize the resulting cytoskeletal protein as well as cell shape and attachment changes in both normal trabecular meshwork (TM) and SC cells, and in cells where various key cytoskeletal proteins such as rho, myosin light chain kinase and phosphatase, and focal adhesion kinase (FAK) have been either constitutively overexpressed, underexpressed, or rendered inactive by dominant negative mutant technology in both flow/no flow and stretching experiments. 2)To reevaluate the cell shape, attachment, contraction, and cytoskeletal protein staining effects of ECA, indacrinone, ticrynafen, vinblastine, cytochalasin B, H-7 and BDM in both TM and now SC cells that similarly over- or underexpress these key cytoskeletal proteins, as in 1. 3)For both 1 and 2 to correlate these findings with quantitative aqueous humor outflow and morphological studies of excised porcine and especially, organ cultured human eyes (anterior segments). The PI believes that these studies will potentially provide important new insight into both the modulation of normal outflow pathway cell function, and abnormal function that might be present in certain glaucomas.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
Project #
Application #
Study Section
Visual Sciences A Study Section (VISA)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Duke University
Schools of Medicine
United States
Zip Code
Gonzalez, Pedro; Li, Guorng; Qiu, Jianming et al. (2014) Role of microRNAs in the trabecular meshwork. J Ocul Pharmacol Ther 30:128-37
Huang, Wei; Li, Guorong; Qiu, Jianming et al. (2013) Protective effects of resveratrol in experimental retinal detachment. PLoS One 8:e75735
Luna, Coralia; Li, Guorong; Huang, Jianyong et al. (2012) Regulation of trabecular meshwork cell contraction and intraocular pressure by miR-200c. PLoS One 7:e51688
Wu, Jing; Li, Guorong; Luna, Coralia et al. (2012) Endogenous production of extracellular adenosine by trabecular meshwork cells: potential role in outflow regulation. Invest Ophthalmol Vis Sci 53:7142-8
Kumar, Janardan; Epstein, David L (2011) Rho GTPase-mediated cytoskeletal organization in Schlemm's canal cells play a critical role in the regulation of aqueous humor outflow facility. J Cell Biochem 112:600-6
Luna, Coralia; Li, Guorong; Qiu, Jianming et al. (2011) Cross-talk between miR-29 and transforming growth factor-betas in trabecular meshwork cells. Invest Ophthalmol Vis Sci 52:3567-72
Luna, Coralia; Li, Guorong; Qiu, Jianming et al. (2011) MicroRNA-24 regulates the processing of latent TGFýý1 during cyclic mechanical stress in human trabecular meshwork cells through direct targeting of FURIN. J Cell Physiol 226:1407-14
Li, Guorong; Luna, Coralia; Qiu, Jianming et al. (2011) Role of miR-204 in the regulation of apoptosis, endoplasmic reticulum stress response, and inflammation in human trabecular meshwork cells. Invest Ophthalmol Vis Sci 52:2999-3007
Li, Guorong; Luna, Coralia; Navarro, Iris D et al. (2011) Resveratrol prevention of oxidative stress damage to lens epithelial cell cultures is mediated by forkhead box O activity. Invest Ophthalmol Vis Sci 52:4395-401
Li, Guorong; Luna, Coralia; Qiu, Jianming et al. (2010) Targeting of integrin beta1 and kinesin 2alpha by microRNA 183. J Biol Chem 285:5461-71

Showing the most recent 10 out of 97 publications