PXD008911

PXD008911 is an original dataset announced via ProteomeXchange.

Title	Differential proteomes in the vitreous of mice with a chronic hypoxic response in photoreceptors
Description	Reduced oxygenation of photoreceptors and the RPE in the ageing eye may be a risk factor for the development of both neovascular and dry AMD. Chronic activation of the molecular response to hypoxia in RPE or photoreceptors leads to retinal degeneration that depends on hypoxia inducible transcription factors. For approaching the identification of accessible markers characteristic for photoreceptors with an activated hypoxic response, we used a proteomics approach to determine the protein composition of the vitreous humor in mice. To discriminate between rod and cone-specific effects we used genetically modified mice that had the hypoxic response activated specifically in rods of a rod-dominant retina (rodΔVhl) or a genetically engineered all-cone retina (coneΔVhl). For comparison, we used wild-type mice exposed for 6 hours to acute hypoxia. We identified 1,357 unique proteins in the vitreous of mice after acute hypoxia, 1,624 in rodΔVhl and 1,895 in coneΔVhl mice. Of these, 1,043 proteins were common to all three types of mice. Of the identified proteins, 257 were significantly regulated by a factor of 1.5 or more in hypoxic mice, 258 in rodΔVhl and 356 in coneΔVhl mice in at least one of the three analyzed time points. Only 51 of the significantly regulated proteins were common to the vitreous of rodΔVhl and coneΔVhl mice, suggesting different consequences of the activated hypoxic response for rods and cones. Guanylate binding protein 2 (GBP2) was found at increased levels in the vitreous of both rodΔVhl and coneΔVhl mice at all time points tested. This was also reflected by increased gene expression in the retina. Although retinal expression of the AMD-associated gene alpha-2 macroglobulin (A2M) appeared increased in both types of mice, the protein was only found elevated in the vitreous of rodΔVhl mice. Other proteins found increased included Serpina3n, synaptosome associated protein 25 (SNAP25) and others. The distinct protein compositions present at early and late time points, suggest a well-regulated process in our models. We hypothesize that some of the proteins identified at early time points may potentially be used as markers for the chronic hypoxic response of photoreceptors.
HostingRepository	PRIDE
AnnounceDate	2019-06-12
AnnouncementXML	Submission_2019-06-13_01:31:01.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Christian Schori
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2018-02-09 05:39:40	ID requested
1	2019-06-12 05:46:09	announced
⏵ 2	2019-06-13 01:31:02	announced	Updated publication reference for PubMed record(s): 31181196.

Schori C, Trachsel C, Grossmann J, Barben M, Klee K, Storti F, Samardzija M, Grimm C, A chronic hypoxic response in photoreceptors alters the vitreous proteome in mice. Exp Eye Res, 185():107690(2019) [pubmed]

curator keyword: Biological

submitter keyword: Vitreous, hypoxic response, shot-gun proteomics, rods, cones, retinal degeneration, AMD

Christian Grimm
contact affiliation	Lab for Retinal Cell Biology Dept. Ophthalmology USZ / UZH University of Zurich
contact email	cgrimm@opht.uzh.ch
lab head
Christian Schori
contact affiliation	University of Zurich
contact email	christian.schori@usz.ch
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD008911
     1. Label: PRIDE project
     2. Name: Differential proteomes in the vitreous of mice with a chronic hypoxic response in photoreceptors