Journal article
Proteomic analysis of the human retina reveals region-specific susceptibilities to metabolic- and oxidative stress-related diseases
PloS one, Vol.13(2), pp.e0193250-e0193250
2018
DOI: 10.1371/journal.pone.0193250
PMCID: PMC5821407
PMID: 29466423
Abstract
Differences in regional protein expression within the human retina may explain molecular predisposition of specific regions to ophthalmic diseases like age-related macular degeneration, cystoid macular edema, retinitis pigmentosa, and diabetic retinopathy. To quantify protein levels in the human retina and identify patterns of differentially-expressed proteins, we collected foveomacular, juxta-macular, and peripheral retina punch biopsies from healthy donor eyes and analyzed protein content by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Protein expression was analyzed with 1-way ANOVA, gene ontology, pathway representation, and network analysis. We identified a mean of 1,974 proteins in the foveomacular retina, 1,999 in the juxta-macular retina, and 1,779 in the peripheral retina. Six hundred ninety-seven differentially-expressed proteins included those unique to and abundant in each anatomic region. Proteins with higher expression in each region include: heat-shock protein 90-alpha (HSP90AA1), and pyruvate kinase (PKM) in the foveomacular retina; vimentin (VIM) and fructose-bisphosphate aldolase C (ALDOC); and guanine nucleotide-binding protein subunit beta-1 (GNB1) and guanine nucleotide-binding protein subunit alpha-1 (GNAT1) in the peripheral retina. Pathway analysis identified downstream mediators of the integrin signaling pathway to be highly represented in the foveomacular region (P = 6.48 e-06). Metabolic pathways were differentially expressed among all retinal regions. Gene ontology analysis showed that proteins related to antioxidant activity were higher in the juxta-macular and the peripheral retina, but present in lower amounts in the foveomacular retina. Our proteomic analysis suggests that certain retinal regions are susceptible to different forms of metabolic and oxidative stress. The findings give mechanistic insight into retina function, reveal important molecular processes, and prioritize new pathways for therapeutic targeting.
Details
- Title: Subtitle
- Proteomic analysis of the human retina reveals region-specific susceptibilities to metabolic- and oxidative stress-related diseases
- Creators
- Gabriel Velez - Medical Scientist Training Program, University of Iowa, Iowa City, Iowa, United States of AmericaDaniel A Machlab - Omics Laboratory, Stanford University, Palo Alto, California, United States of AmericaPeter H Tang - Palo Alto Veterans Administration, Palo Alto, California, United States of AmericaYang Sun - Palo Alto Veterans Administration, Palo Alto, California, United States of AmericaStephen H Tsang - Department of Pathology & Cell Biology, College of Physicians & Surgeons, Columbia University, New York, New York, United States of AmericaAlexander G Bassuk - Department of Pediatrics, University of Iowa, Iowa City, Iowa, United States of AmericaVinit B Mahajan - Palo Alto Veterans Administration, Palo Alto, California, United States of America
- Resource Type
- Journal article
- Publication Details
- PloS one, Vol.13(2), pp.e0193250-e0193250
- DOI
- 10.1371/journal.pone.0193250
- PMID
- 29466423
- PMCID
- PMC5821407
- NLM abbreviation
- PLoS One
- ISSN
- 1932-6203
- eISSN
- 1932-6203
- Publisher
- Public Library of Science; United States
- Grant note
- R01 EY025225 / NEI NIH HHS R01 EY025295 / NEI NIH HHS R01 EY018213 / NEI NIH HHS P30 CA013696 / NCI NIH HHS T32 GM007337 / NIGMS NIH HHS R01 EY024698 / NEI NIH HHS I01 CX001481 / CSRD VA R01 EY026682 / NEI NIH HHS R01 EY024665 / NEI NIH HHS R21 AG050437 / NIA NIH HHS K08 EY022058 / NEI NIH HHS P30 EY019007 / NEI NIH HHS
- Language
- English
- Date published
- 2018
- Academic Unit
- Neurology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Neurology (Pediatrics)
- Record Identifier
- 9984070659202771
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