Dataset Information

Diabetes-related changes in the protein composition and the biomechanical properties of human retinal vascular basement membranes.

ABSTRACT: Basement membranes (BMs) are specialized sheets of extracellular matrix that outline epithelial cell layers, muscle fibers, blood vessels, and peripheral nerves. A well-documented histological hallmark of progressing diabetes is a major increase in vascular BM thickness. In order to investigate whether this structural change is accompanied by a change in the protein composition, we compared the proteomes of retinal vascular BMs from diabetic and non-diabetic donors by using LC-MS/MS. Data analysis showed that seventeen extracellular matrix (ECM)-associated proteins were more abundant in diabetic than non-diabetic vascular BMs. Four ECM proteins were more abundant in non-diabetic than in diabetic BMs. Most of the over-expressed proteins implicate a complement-mediated chronic inflammatory process in the diabetic retinal vasculature. We also found an up-regulation of norrin, a protein that is known to promote vascular proliferation, possibly contributing to the vascular remodeling during diabetes. Many of the over-expressed proteins were localized to microvascular aneurisms. Further, the overall stoichiometry of proteins was changed, such that the relative abundance of collagens in BMs from diabetic patients was higher than normal. Biomechanical measurements of vascular BM flat mounts using AFM showed that their outer surface was softer than normal.

SUBMITTER: Halfter W

PROVIDER: S-EPMC5746242 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Diabetes-related changes in the protein composition and the biomechanical properties of human retinal vascular basement membranes.

Halfter Willi W Moes Suzette S Asgeirsson Daphne O DO Halfter Kathrin K Oertle Philipp P Melo Herraiz Esther E Plodinec Marija M Jenoe Paul P Henrich Paul Bernhard PB

PloS one 20171228 12

Basement membranes (BMs) are specialized sheets of extracellular matrix that outline epithelial cell layers, muscle fibers, blood vessels, and peripheral nerves. A well-documented histological hallmark of progressing diabetes is a major increase in vascular BM thickness. In order to investigate whether this structural change is accompanied by a change in the protein composition, we compared the proteomes of retinal vascular BMs from diabetic and non-diabetic donors by using LC-MS/MS. Data analys ...[more]

PMID: 29284024

Similar Datasets

Project description:Diabetes associated complications, including diabetic retinopathy and loss of vision, are major health concerns. Detecting early retinal vascular changes during diabetes is not well documented, and only few studies have addressed this domain. The purpose of this study was to noninvasively evaluate temporal changes in retinal vasculature at very early stages of diabetes using fundus images from preclinical models of diabetes. Non-diabetic and Akita/+ male mice with different duration of diabetes were subjected to fundus imaging using a Micron III imaging system. The images were obtained from 4 weeks- (onset of diabetes), 8 weeks-, 16 weeks-, and 24 weeks-old male Akita/+ and non-diabetic mice. In total 104 fundus images were subjected to analysis for various feature extractions. A combination of Canny Edge Detector and Angiogenesis Analyzer plug-ins in ImageJ were utilized to quantify various retinal vascular changes in fundus images. Statistical analyses were conducted to determine significant differences in the various extracted features from fundus images of diabetic and non-diabetic animals. Our novel image analysis method led to extraction of over 20 features. These results indicated that some of these features were significantly changed with a short duration of diabetes, and others remained the same but changed after longer duration of diabetes. These patterns likely distinguish acute (protective) and chronic (damaging) associated changes with diabetes. We show that with a combination of various plugging one can extract over 20 features from retinal vasculature fundus images. These features change during diabetes, thus allowing the quantification of quality of retinal vascular architecture as biomarkers for disease progression. In addition, our method was able to identify unique differences among diabetic mice with different duration of diabetes. The ability to noninvasively detect temporal retinal vascular changes during diabetes could lead to identification of specific markers important in the development and progression of diabetes mediated-microvascular changes, evaluation of therapeutic interventions, and eventual reversal of these changes in order to stop or delay disease progression.

Dataset Information

Diabetes-related changes in the protein composition and the biomechanical properties of human retinal vascular basement membranes.

Publications

Diabetes-related changes in the protein composition and the biomechanical properties of human retinal vascular basement membranes.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets