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Proteomic approach to new drugable targets of retinal neovascularization
Author(s) -
Vähätupa Maria
Publication year - 2019
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2019.8085
Subject(s) - retinopathy of prematurity , retinal , downregulation and upregulation , neovascularization , proteome , retina , crystallin , retinopathy , diabetic retinopathy , angiogenesis , medicine , ophthalmology , biology , bioinformatics , cancer research , neuroscience , biochemistry , endocrinology , diabetes mellitus , genetics , pregnancy , gene , gestational age
Retinal neovascular diseases such as retinopathy of prematurity (ROP), proliferative diabetic retinopathy (PDR) and retinal vein occlusion (RVO) are major causes of visual impairment in western countries. Oxygen‐induced retinopathy (OIR) model is widely used model for studying these retinopathies. The purpose of our study was to characterize changes in protein levels during OIR model using by a recently developed technique, sequential window acquisition of all theoretical mass spectra (SWATH‐MS) proteomics. Samples from normoxic and OIR animals were collected in three time points; P13, P17 and P42 and analyzed with SWATH‐MS. Immunoblotting and immunohistochemistry from mouse and human PDR samples was used to confirm these results and address their relevance for human neovascular retinopathies. We performed the most extensive proteomic profiling of OIR to date and quantified almost 3000 unique proteins and their expression levels in control and OIR retinas. The methodology used in the study allowed also temporal profiling of OIR proteome. The most prominent group of proteins induced at the early hypoxic phase of OIR were crystallins, while angiogenesis related proteins such as Filamin A and B, Annexin 2 and Myosin 9 were upregulated at the peak of neovascularization. In addition, the upstream regulator analysis identified potentially upregulated enhancers of angiogenesis, among them TGF‐β1. As retinal neovascularization regresses later in OIR, majority of the changes seen in protein expression levels returned to normal at P42, but there was still evidence suggesting that proteins involved in neurotransmission stayed at reduced levels.