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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Tezel, Gülgün Luo, Cheng Kuehn, Markus H. Yang, Xiangjun Yu, Dahai Cai, Jian Powell, David W. |
| Description | Country affiliation: United States Author Affiliation: Yang X ( Department of Ophthalmology and Visual Sciences, University of Louisville School of Medicine, Louisville, Kentucky 40202, USA.) |
| Abstract | PURPOSE: This study aimed to determine retinal proteomic alterations in human glaucoma, with particular focus on links to TNF- /TNFR1 signaling. METHODS: Human retinal protein samples were obtained from 20 donors with (n = 10) or without (n = 10) glaucoma. Alterations in protein expression were individually analyzed by quantitative LC-MS/MS. Quantitative Western blot analysis with cleavage or phosphorylation site-specific antibodies was used for data validation, and cellular localization of selected proteins was determined by immunohistochemical analysis of the retina in an additional group of glaucomatous human donor eyes (n = 38) and nonglaucomatous controls (n = 30). RESULTS: Upregulated retinal proteins in human glaucoma included a number of downstream adaptor/interacting proteins and protein kinases involved in TNF- /TNFR1 signaling. Bioinformatic analysis of the high-throughput data established extended networks of diverse functional interactions with death-promoting and survival-promoting pathways and mediation of immune response. Upregulated pathways included death receptor-mediated caspase cascade, mitochondrial dysfunction, endoplasmic reticulum stress, calpains leading to apoptotic cell death, NF-κB and JAK/STAT pathways, and inflammasome-assembly mediating inflammation. Interestingly, retinal expression pattern of a regulator molecule, TNFAIP3, exhibited prominent variability between individual samples, and methylation of cytosine nucleotides in the TNFAIP3 promoter was found to be correlated with this variability among glaucomatous donors. CONCLUSIONS: Findings of this study reveal a number of proteins upregulated in the glaucomatous human retina that exhibit many links to TNF- /TNFR1 signaling. By highlighting various signaling molecules and regulators involved in cell death and immune response pathways and by correlating proteomic findings with epigenetic alterations, these findings provide a framework motivating further research. |
| ISSN | 01460404 |
| e-ISSN | 15525783 |
| DOI | 10.1167/iovs.11-8152 |
| Journal | Investigative Opthalmology & Visual Science |
| Issue Number | 11 |
| Volume Number | 52 |
| Language | English |
| Publisher | Association for Research in Vision and Ophthalmology |
| Publisher Date | 2011-10-31 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Glaucoma Metabolism Nerve Degeneration Optic Nerve Diseases Receptors, Tumor Necrosis Factor, Type I Retina Signal Transduction Physiology Tumor Necrosis Factor-alpha Blotting, Western Caspases Chromatography, Liquid Computational Biology Dna Methylation Dna Primers Eye Proteins Fluorescent Antibody Technique, Indirect Janus Kinases Nf-kappa B Polymorphism, Single Nucleotide Proteomics Receptors, Death Domain Stat Transcription Factors Tandem Mass Spectrometry Up-regulation Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't Discipline Ophthalmology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Ophthalmology Sensory Systems Cellular and Molecular Neuroscience |
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