PURPOSE: To identify differentially expressed glycogenes in trabecular meshwork (TM) of eyes with primary open-angle glaucoma (POAG). METHODS: Total RNA was isolated from TM of cadaveric eyes derived from donors with diagnosed glaucomas of different etiologies and from normal control subjects. RNA was amplified and hybridized to the GLYCOv2 oligonucleotide microarray that contains probes for carbohydrate-binding proteins, glycosyltransferases, and other genes involved in the regulation of glycosylation. Statistical analysis was used to identify differentially expressed genes between normal and POAG samples. RESULTS: This study revealed that POAG TM and normal TM have distinct gene expression profiles. Of the 2001 genes on the array, 19 genes showed differential expression of greater than 1.4-fold in POAG. Mimecan and activinA, which have been shown to be upregulated in models of glaucoma, were both found to be elevated in POAG TM. Many genes were identified for the first time to be differentially regulated in POAG. Among the upregulated genes were: (1) cell adhesion molecules including platelet endothelial cell adhesion molecule-1 and P-selectin, both of which are targets of NFkappaB, which has been shown to be activated in glaucomatous TM; (2) lumican, a core protein of keratan sulfate proteoglycans; and (3) the receptor for IL6, a cytokine that has been shown to be upregulated in TM in response to elevated intraocular pressure. Among the downregulated genes were chondroitin-4-O-sulfotransferase involved in the synthesis of chondroitin sulfate chains and the receptor for PDGFbeta, a growth factor that has been shown to stimulate both TM cell proliferation and phagocytic activity. Results for several genes were confirmed by RTq-PCR. CONCLUSIONS: Microarray technology was used to show, for the first time, that POAG TM has a distinct glycogene expression profile. Differentially expressed glycogenes identified in this study have not been previously investigated for their role in the pathogenesis of POAG and thus are novel factors for further study of the mechanism of the disease and for their possible use as diagnostic markers.
PURPOSE: To identify differentially expressed glycogenes in trabecular meshwork (TM) of eyes with primary open-angle glaucoma (POAG). METHODS: Total RNA was isolated from TM of cadaveric eyes derived from donors with diagnosed glaucomas of different etiologies and from normal control subjects. RNA was amplified and hybridized to the GLYCOv2 oligonucleotide microarray that contains probes for carbohydrate-binding proteins, glycosyltransferases, and other genes involved in the regulation of glycosylation. Statistical analysis was used to identify differentially expressed genes between normal and POAG samples. RESULTS: This study revealed that POAG TM and normal TM have distinct gene expression profiles. Of the 2001 genes on the array, 19 genes showed differential expression of greater than 1.4-fold in POAG. Mimecan and activinA, which have been shown to be upregulated in models of glaucoma, were both found to be elevated in POAG TM. Many genes were identified for the first time to be differentially regulated in POAG. Among the upregulated genes were: (1) cell adhesion molecules including platelet endothelial cell adhesion molecule-1 and P-selectin, both of which are targets of NFkappaB, which has been shown to be activated in glaucomatous TM; (2) lumican, a core protein of keratan sulfate proteoglycans; and (3) the receptor for IL6, a cytokine that has been shown to be upregulated in TM in response to elevated intraocular pressure. Among the downregulated genes were chondroitin-4-O-sulfotransferase involved in the synthesis of chondroitin sulfate chains and the receptor for PDGFbeta, a growth factor that has been shown to stimulate both TM cell proliferation and phagocytic activity. Results for several genes were confirmed by RTq-PCR. CONCLUSIONS: Microarray technology was used to show, for the first time, that POAG TM has a distinct glycogene expression profile. Differentially expressed glycogenes identified in this study have not been previously investigated for their role in the pathogenesis of POAG and thus are novel factors for further study of the mechanism of the disease and for their possible use as diagnostic markers.
Authors: Yuk Fai Leung; Pancy Oi Sin Tam; Wing Shan Lee; Dennis Shun Chiu Lam; Hin Fai Yam; Bao Jian Fan; Clement Chee Yung Tham; John Kien Han Chua; Chi Pui Pang Journal: Mol Vis Date: 2003-09-05 Impact factor: 2.367
Authors: N Kojima; B A Fenderson; M R Stroud; R I Goldberg; R Habermann; T Toyokuni; S Hakomori Journal: Glycoconj J Date: 1994-06 Impact factor: 2.916
Authors: Ted S Acott; Mary J Kelley; Kate E Keller; Janice A Vranka; Diala W Abu-Hassan; Xinbo Li; Mini Aga; John M Bradley Journal: J Ocul Pharmacol Ther Date: 2014-01-08 Impact factor: 2.671
Authors: Shinwu Jeong; Nitin Patel; Christopher K Edlund; Jaana Hartiala; Dennis J Hazelett; Tatsuo Itakura; Pei-Chang Wu; Robert L Avery; Janet L Davis; Harry W Flynn; Geeta Lalwani; Carmen A Puliafito; Hussein Wafapoor; Minako Hijikata; Naoto Keicho; Xiaoyi Gao; Pablo Argüeso; Hooman Allayee; Gerhard A Coetzee; Mathew T Pletcher; David V Conti; Stephen G Schwartz; Alexander M Eaton; M Elizabeth Fini Journal: Invest Ophthalmol Vis Sci Date: 2015-04 Impact factor: 4.799
Authors: Adam E Sienkiewicz; Brandon N Rosenberg; Genea Edwards; Teresia A Carreon; Sanjoy K Bhattacharya Journal: Proteomics Clin Appl Date: 2014-03-07 Impact factor: 3.494
Authors: Yutao Liu; R Rand Allingham; Xuejun Qin; David Layfield; Andrew E Dellinger; Jason Gibson; Joshua Wheeler; Allison E Ashley-Koch; W Daniel Stamer; Michael A Hauser Journal: Invest Ophthalmol Vis Sci Date: 2013-09-27 Impact factor: 4.799
Authors: M Elizabeth Fini; Stephen G Schwartz; Xiaoyi Gao; Shinwu Jeong; Nitin Patel; Tatsuo Itakura; Marianne O Price; Francis W Price; Rohit Varma; W Daniel Stamer Journal: Prog Retin Eye Res Date: 2016-09-22 Impact factor: 21.198