Journal article
Proteomics Analysis of Molecular Risk Factors in the Ocular Hypertensive Human Retina
Investigative ophthalmology & visual science, Vol.56(10), pp.5816-5830
09/2015
DOI: 10.1167/iovs.15-17294
PMCID: PMC4566415
PMID: 26348630
Abstract
To better understand ocular hypertension-induced early molecular alterations that may determine the initiation of neurodegeneration in human glaucoma, this study analyzed retinal proteomic alterations in the ocular hypertensive human retina. Retina samples were obtained from six human donors with ocular hypertension (without glaucomatous injury) and six age- and sex-matched normotensive controls. Retinal proteins were analyzed by two-dimensional LC-MS/MS (liquid chromatography and linear ion trap mass spectrometry) using oxygen isotope labeling for relative quantification of protein expression. Proteomics data were validated by Western blot and immunohistochemical analyses of selected proteins. Out of over 2000 retinal proteins quantified, hundreds exhibited over 2-fold increased or decreased expression in ocular hypertensive samples relative to normotensive controls. Bioinformatics linked the proteomics datasets to various pathways important for maintenance of cellular homeostasis in the ocular hypertensive retina. Upregulated proteins included various heat shock proteins, ubiquitin proteasome pathway components, antioxidants, and DNA repair enzymes, while many proteins involved in mitochondrial oxidative phosphorylation exhibited downregulation in the ocular hypertensive retina. Despite the altered protein expression reflecting intrinsic adaptive/protective responses against mitochondrial energy failure, oxidative stress, and unfolded proteins, no alterations suggestive of an ongoing cell death process or neuroinflammation were detectable. This study provides information about ocular hypertension-related molecular risk factors for glaucoma development. Molecular alterations detected in the ocular hypertensive human retina as opposed to previously detected alterations in human donor retinas with clinically manifest glaucoma suggest that proteome alterations determine the individual threshold to tolerate the ocular hypertension-induced tissue stress or convert to glaucomatous neurodegeneration when intrinsic adaptive/protective responses are overwhelmed.
Details
- Title: Subtitle
- Proteomics Analysis of Molecular Risk Factors in the Ocular Hypertensive Human Retina
- Creators
- Xiangjun Yang - Columbia UniversityGözde Hondur - Columbia UniversityMing Li - University of LouisvilleJian Cai - University of LouisvilleJon B Klein - University of LouisvilleMarkus H Kuehn - University of Iowa, Ophthalmology and Visual SciencesGülgün Tezel - Columbia University
- Resource Type
- Journal article
- Publication Details
- Investigative ophthalmology & visual science, Vol.56(10), pp.5816-5830
- Publisher
- United States
- DOI
- 10.1167/iovs.15-17294
- PMID
- 26348630
- PMCID
- PMC4566415
- ISSN
- 0146-0404
- eISSN
- 1552-5783
- Grant note
- 1R21EY024105 / NEI NIH HHS R21 EY024105 / NEI NIH HHS R01 EY022044 / NEI NIH HHS
- Language
- English
- Date published
- 09/2015
- Academic Unit
- Ophthalmology and Visual Sciences
- Record Identifier
- 9983980049202771
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