Affiliation:
1. Faculty of Medicine and Health Technology, Tampere University, 33521 Tampere, Finland
2. Tampere University Hospital, 33520 Tampere, Finland
Abstract
Small GTPase R-Ras regulates vascular permeability in angiogenesis. In the eye, abnormal angiogenesis and hyperpermeability are the leading causes of vision loss in several ischemic retinal diseases such as proliferative diabetic retinopathy (PDR), retinal vein occlusion (RVO), and retinopathy of prematurity (ROP). Oxygen-induced retinopathy (OIR) is the most widely used experimental model for these ischemic retinopathies. To shed more light on how the R-Ras regulates vascular permeability in pathological angiogenesis, we performed a comprehensive (>2900 proteins) characterization of OIR in R-Ras knockout (KO) and wild-type (WT) mice by sequential window acquisition of all theoretical mass spectra (SWATH-MS) proteomics. OIR and age-matched normoxic control retinas were collected at P13, P17, and P42 from R-Ras KO and WT mice and were subjected to SWATH-MS and data analysis. The most significant difference between the R-Ras KO and WT retinas was an accumulation of plasma proteins. The pathological vascular hyperpermeability during OIR in the R-Ras KO retina took place very early, P13. This led to simultaneous hypoxic cell injury/death (ferroptosis), glycolytic metabolism as well compensatory mechanisms to counter the pathological leakage from angiogenic blood vessels in the OIR retina of R-Ras deficient mice.
Funder
Competitive State Research Financing of the Expert Responsibility Area of Tampere University Hospital
Academy of Finland
Finnish Diabetic Research Foundation
Diabetes Wellness Foundation
Tampere Tuberculosis Foundation
Pirkanmaa Hospital District Research Foundation
Finnish Eye Foundation
Finnish Cultural Foundation
Mary and Georg C. Ehrnrooth’s Foundation
Päivikki and Sakari Sohlberg Foundation
Elsemay Björn Fund
TEKES
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis