SWATH-MS Proteomic Analysis of Oxygen-Induced Retinopathy Reveals Novel Potential Therapeutic Targets

Oxygen-induced retinopathy (OIR) is the most widely used model for ischemic retinopathies such as retinopathy of prematurity (ROP), proliferative diabetic retinopathy (PDR), and retinal vein occlusion (RVO). The purpose of this study was to perform the most comprehensive characterization of OIR by a...

Full description

Saved in:
Bibliographic Details
Published in:Investigative ophthalmology & visual science 2018-07, Vol.59 (8), p.3294-3306
Main Authors: Vähätupa, Maria, Nättinen, Janika, Jylhä, Antti, Aapola, Ulla, Kataja, Marko, Kööbi, Peeter, Järvinen, Tero A H, Uusitalo, Hannu, Uusitalo-Järvinen, Hannele
Format: Article
Language:English
Subjects:
Adult
Animals
Blotting, Western
Diabetic Retinopathy - metabolism
Eye Proteins - metabolism
Humans
Immunohistochemistry
Mass Spectrometry - methods
Mice, Inbred C57BL
Microscopy, Confocal
Middle Aged
Oxygen - toxicity
Proteome - metabolism
Proteomics - methods
Retina - metabolism
Retinal Neovascularization - metabolism
Retinal Vein Occlusion - metabolism
Retinopathy of Prematurity - chemically induced
Retinopathy of Prematurity - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Oxygen-induced retinopathy (OIR) is the most widely used model for ischemic retinopathies such as retinopathy of prematurity (ROP), proliferative diabetic retinopathy (PDR), and retinal vein occlusion (RVO). The purpose of this study was to perform the most comprehensive characterization of OIR by a recently developed technique, sequential window acquisition of all theoretical mass spectra (SWATH-MS) proteomics. Control and OIR retina samples collected from various time points were subjected to SWATH-MS and detailed data analysis. Immunohistochemistry from mouse retinas as well as neovascular membranes from human PDR and RVO patients were used for the detection of the localization of the proteins showing altered expression in the retina and to address their relevance to human ischemic retinopathies. We report the most extensive proteomic profiling of OIR to date by quantifying almost 3000 unique proteins and their expression differences between control and OIR retinas. Crystallins were the most prominent proteins induced by hypoxia in the retina, while angiogenesis related proteins such as Filamin A and nonmuscle myosin IIA stand out at the peak of angiogenesis. Majority of the changes in protein expression return to normal at P42, but there is evidence to suggest that proteins involved in neurotransmission remain at reduced level. The results reveal new potential therapeutic targets to address hypoxia-induced pathological angiogenesis taking place in number of retinal diseases. The extensive proteomic profiling combined with pathway analysis also identifies novel molecular networks that could contribute to the pathogenesis of retinal diseases.
ISSN:1552-5783
1552-5783
DOI:10.1167/iovs.18-23831