The primary hypothesis in this proposal is that intraocular IOP is regulated by two intrinsic mechanisms: the paracrine action of ocular purines and mechanical stretch of the trabecular meshwork.
Three specific aims will be used to explore this hypothesis. In the first aim the Dr. Crosson's studies in purinergic regulation of aqueous humor dynamics will be extended to analysis of purinergic P2 agonists effects on intraocular pressure, aqueous flow and outflow facility. In the second specific aim the purinergic regulation of trabecular cell function will be evaluated. This will include studying purinergic modulation of MAP kinase pathways, cross talk between purinergic and other receptor systems and purinergic modulation of matrix metalloproteinase secretion and transcription. In the last specific aim the response of trabecular meshwork cells to stretch will be evaluated. The results from this work are predicted to 1) improve understanding of the physiological systems that regulate aqueous humor dynamics, 2) identify the signal transduction pathways that mediate purinergic and stretch-induced changes in trabecular meshwork cells and 3) develop a rational basis for the use of purinergic agonists in the treatment of glaucoma.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY009741-11
Application #
6635624
Study Section
Special Emphasis Panel (ZRG1-SSS-R (03))
Program Officer
Liberman, Ellen S
Project Start
1993-03-01
Project End
2006-02-28
Budget Start
2003-03-01
Budget End
2004-02-29
Support Year
11
Fiscal Year
2003
Total Cost
$331,990
Indirect Cost
Name
Medical University of South Carolina
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
183710748
City
Charleston
State
SC
Country
United States
Zip Code
29425
Dahrouj, Mohammad; Alsarraf, Oday; Liu, Yueying et al. (2013) C-type natriuretic peptide protects the retinal pigment epithelium against advanced glycation end product-induced barrier dysfunction. J Pharmacol Exp Ther 344:96-102
Ablonczy, Zsolt; Dahrouj, Mohammad; Tang, Peter H et al. (2011) Human retinal pigment epithelium cells as functional models for the RPE in vivo. Invest Ophthalmol Vis Sci 52:8614-20
Webb, Jerry G; Yang, Xiaofeng; Crosson, Craig E (2011) Bradykinin activation of extracellular signal-regulated kinases in human trabecular meshwork cells. Exp Eye Res 92:495-501
Crosson, Craig E; Mani, Santhosh K; Husain, Shahid et al. (2010) Inhibition of histone deacetylase protects the retina from ischemic injury. Invest Ophthalmol Vis Sci 51:3639-45
Husain, Shahid; Potter, David E; Crosson, Craig E (2009) Opioid receptor-activation: retina protected from ischemic injury. Invest Ophthalmol Vis Sci 50:3853-9
Webb, Jerry G; Yang, Xiaofeng; Crosson, Craig E (2009) Expression of the kallikrein/kinin system in human anterior segment. Exp Eye Res 89:126-32
Ablonczy, Zsolt; Prakasam, Annamalai; Fant, James et al. (2009) Pigment epithelium-derived factor maintains retinal pigment epithelium function by inhibiting vascular endothelial growth factor-R2 signaling through gamma-secretase. J Biol Chem 284:30177-86
Husain, Shahid; Crosson, Craig E (2008) Role of PKCepsilon in PGF2alpha-stimulated MMP-2 secretion from human ciliary muscle cells. J Ocul Pharmacol Ther 24:268-77
Husain, Shahid; Yates, Phillip W; Crosson, Craig E (2008) Latanoprost-induced changes in rat intraocular pressure: direct or indirect? J Ocul Pharmacol Ther 24:367-72
Ablonczy, Zsolt; Crosson, Craig E (2007) VEGF modulation of retinal pigment epithelium resistance. Exp Eye Res 85:762-71

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