Journal article
Proteomic Landscape of the Human Choroid-Retinal Pigment Epithelial Complex
JAMA ophthalmology, Vol.132(11), pp.1271-1281
11/01/2014
DOI: 10.1001/jamaophthalmol.2014.2065
PMID: 25058583
Abstract
IMPORTANCE Differences in geographical protein expression in the human choroid-retinal pigment epithelial (RPE) complexmay explain molecular predisposition of regions to ophthalmic diseases such as age-related macular degeneration.
OBJECTIVE To characterize the proteome of the human choroid-RPE complex and to identify differentially expressed proteins in specific anatomic regions.
DESIGN, SETTING, AND PARTICIPANTS Experimental study of choroid-RPE tissue from 3 nondiseased eyes. The choroid-RPE complex underwent biopsy from beneath the foveal, macular, and peripheral retina. Protein fractions were isolated and subjected to multidimensional liquid chromatography and tandem mass spectrometry. A bioinformatic pipeline matched peptide spectra to the human proteome, assigned gene ontology classification, and identified protein signaling pathways unique to each of the choroid-RPE regions.
MAIN OUTCOMES AND MEASURES Mean number of mass spectra, statistically significant differentially expressed proteins, gene ontology classification, and pathway representation.
RESULTS We identified a mean of 4403 unique proteins in each of the foveal, macular, and peripheral choroid-RPE tissues. Six hundred seventy-one differentially expressed proteins included previously known risk factors for retinal diseases related to oxidative stress, inflammation, and the complement cascade. Gene ontology analysis showed that unique categories in the foveal and macular regions included immune process proteins as well as protein complexes and plasma membrane proteins. The peripheral region contained unique antioxidant activity proteins. Many proteins had the highest expression in the foveal or macular regions, including inflammation-related proteins HLA-A, HLA-B, and HLA-C antigens; intercellular adhesion molecule 1 (ICAM-1); S100; transcription factor ERG; antioxidant superoxide dismutase 1 (SOD1); chloride intracellular channel 6 ion (CLIC6); activators of the complement cascade C1q, C6, and C8; and complement factor H. Proteins with higher expression in the periphery included bestrophin 1 (BEST1), transcription factor RNA binding motif protein 39 (RBM39), inflammatory mediator macrophage migration inhibitory factor, antioxidant SOD3, ion channel voltage-dependent anion-selective channel protein 3 (VDAC3), and complement inhibitor CD55. The complement activation was among the highest represented pathways (P < 7.5e-13).
CONCLUSIONS AND RELEVANCE This proteomic data set identifies novel molecular signatures in anatomically sensitive regions of the choroid-RPE complex. The findings give mechanistic insight into choroid-RPE function, reveal important choroid-RPE processes, and prioritize new pathways for therapeutic targeting.
Details
- Title: Subtitle
- Proteomic Landscape of the Human Choroid-Retinal Pigment Epithelial Complex
- Creators
- Jessica M. Skeie - University of IowaVinit B. Mahajan - University of Iowa
- Resource Type
- Journal article
- Publication Details
- JAMA ophthalmology, Vol.132(11), pp.1271-1281
- Publisher
- Amer Medical Assoc
- DOI
- 10.1001/jamaophthalmol.2014.2065
- PMID
- 25058583
- ISSN
- 2168-6165
- eISSN
- 2168-6173
- Number of pages
- 11
- Grant note
- F32EY022280 / NATIONAL EYE INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Eye Institute (NEI) Bright Focus Foundation; BrightFocus Foundation 1F32EY022280-01A1; K08EY020530 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Language
- English
- Date published
- 11/01/2014
- Academic Unit
- Ophthalmology and Visual Sciences
- Record Identifier
- 9984627336502771
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