Glaucoma refers collectively to a group of eye diseases whose molecular basis is poorly understood. Except in """"""""normal-pressure"""""""" glaucoma, the diseases are associated with increased intraocular pressure. Increased resistance to aqueous outflow through the trabecular meshwork (TM) appears to play a key role in the onset and progression of primary open angle glaucoma (POAG). The hypothesis of the proposal is that POAG associated proteins and protein modifications contribute to blockage of aqueous outflow in the TM. Proteomic analyses of TM tissue from in vivo trabeculectomy and left over rim-tissue from cornea transplant will be pursued to determine protein differences between normal and glaucomatous donors. Liquid chromatography tandem mass spectrometry and bioinformatic methods will be used to identify POAG associated protein and protein modifications. In preliminary studies, 4-hydorxynonenal (HNE) and Argpyrimidine oxidative protein modifications appear to be more prevalent in glaucomatous tissue. Furthermore, cochlin, a protein associated with inheritable deafness, has been found only in glaucomatous tissue. Western analysis and immunohistochemistry will be used to probe for differences in protein modifications between normal and glaucomatous TM tissue and verify the prevalence of HNE modification in glaucomatous TM tissue. Western analysis and immunohistochemistry will also be used to test the hypothesis that cochlin is associated with glaucomatous trabecular meshwork plaques/mucopolysaccharide deposits. The long-term goal of this proposal is to better understand mechanisms of glaucoma pathogenesis and facilitate the development of effective therapies for limiting disease progression. ? ?

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Small Research Grants (R03)
Project #
5R03EY015266-04
Application #
7269876
Study Section
Special Emphasis Panel (ZEY1-VSN (01))
Program Officer
Liberman, Ellen S
Project Start
2005-09-01
Project End
2008-08-31
Budget Start
2007-09-01
Budget End
2008-08-31
Support Year
4
Fiscal Year
2007
Total Cost
$148,568
Indirect Cost
Name
University of Miami School of Medicine
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
052780918
City
Coral Gables
State
FL
Country
United States
Zip Code
33146
Suarez, Maria Fernanda; Piqueras, Maria Carmen; Correa, Leandro et al. (2017) Phospholipidomic Studies in Human Cornea From Climatic Droplet Keratopathy. J Cell Biochem 118:3920-3931
Carreon, Teresia A; Castellanos, Aida; Gasull, Xavier et al. (2017) Interaction of cochlin and mechanosensitive channel TREK-1 in trabecular meshwork cells influences the regulation of intraocular pressure. Sci Rep 7:452
Sienkiewicz, Adam E; Rosenberg, Brandon N; Edwards, Genea et al. (2014) Aberrant glycosylation in the human trabecular meshwork. Proteomics Clin Appl 8:130-42
Goel, Manik; Sienkiewicz, Adam E; Picciani, Renata et al. (2012) Cochlin, intraocular pressure regulation and mechanosensing. PLoS One 7:e34309
Goel, Manik; Sienkiewicz, Adam E; Picciani, Renata et al. (2011) Cochlin induced TREK-1 co-expression and annexin A2 secretion: role in trabecular meshwork cell elongation and motility. PLoS One 6:e23070
Lee, Eun Suk; Gabelt, B'ann T; Faralli, Jennifer A et al. (2010) COCH transgene expression in cultured human trabecular meshwork cells and its effect on outflow facility in monkey organ cultured anterior segments. Invest Ophthalmol Vis Sci 51:2060-6
Junk, Anna K; Goel, Manik; Mundorf, Tom et al. (2010) Decreased carbohydrate metabolism enzyme activities in the glaucomatous trabecular meshwork. Mol Vis 16:1286-91
Amelinckx, Adriana; Castello, Maria; Arrieta-Quintero, Esdras et al. (2009) Laser trabeculoplasty induces changes in the trabecular meshwork glycoproteome: a pilot study. J Proteome Res 8:3727-36
Bhattacharya, Sanjoy K (2009) prospects for proteomics Directed Genomic and Genetic Analyses in Disease Discoveries. Proteomics Insights 2:23-26
Bhattacharya, Sanjoy K; Gabelt, B'Ann T; Ruiz, Jose et al. (2009) Cochlin expression in anterior segment organ culture models after TGFbeta2 treatment. Invest Ophthalmol Vis Sci 50:551-9

Showing the most recent 10 out of 22 publications