Objective Diabetic retinopathy (DR) is a major cause of blindness in adults and the underlying pathophysiology includes endothelial dysfunction. Endothelial dysfunction is a perturbation of endothelial homeostasis including changes in endothelial barrier integrity, alterations of the endothelial cell surface, which becomes proinflammatory and mediates increased leukocyte adhesion and changes in endothelial survival functions. Endothelial dysfunction is regulated by an intimate crosstalk of the endothelium with leukocytes and inflammatory pathways of the innate immunity (endothelial-extrinsic pathways), which are activated in the diabetic vasculature affecting the endothelial barrier and leukocyte adhesiveness, and by endothelial cell-intrinsic pathways affecting endothelial survival that are regulated by specific components of the diabetic microenvironement, e.g. hypoxia. The aims of the present proposal are (i) to assess how leukocyte-endothelial interactions (here a particular emphasis will be laid on novel components of the leukocyte adhesion cascade, such as Developmental endothelial locus-1 or Junctional Adhesion Molecule-C, recently identified by the group of the applicant), as well as how macrophage activation/polarization in the local retinal microenvironment affect endothelial homeostasis and dysfunction in the course of DR, and (ii) to investigate pathways regulating survival functions of the endothelium particularly under hypoxic/ischemic conditions in the diabetic retina. The proposal is highly innovative, since the knowledge about these pathways in the context of endothelial dysfunction in DR is scarce. Understanding the molecular contribution of endothelial cell-extrinsic inflammatory pathways and endothelial-cell intrinsic, survival-regulating pathways in the context of DR will have a high impact as it will provide the platform for developing novel specific therapeutic approaches for this major diabetic complication. Fields of science medical and health sciencesbasic medicinephysiologypathophysiologymedical and health sciencesclinical medicineendocrinologydiabetesmedical and health sciencesclinical medicineophthalmologyretinopathymedical and health sciencesbasic medicinephysiologyhomeostasis Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) ERC-SG-LS4 - ERC Starting Grant - Physiology, Pathophysiology and Endocrinology Call for proposal ERC-2011-StG_20101109 See other projects for this call Funding Scheme ERC-SG - ERC Starting Grant Coordinator TECHNISCHE UNIVERSITAET DRESDEN Address Helmholtzstrasse 10 01069 Dresden Germany See on map Region Sachsen Dresden Dresden, Kreisfreie Stadt Activity type Higher or Secondary Education Establishments Principal investigator Triantafyllos Chavakis (Prof.) Administrative Contact Friederieke Noack (Ms.) Links Contact the organisation Opens in new window Website Opens in new window EU contribution No data Beneficiaries (1) Sort alphabetically Sort by EU Contribution Expand all Collapse all TECHNISCHE UNIVERSITAET DRESDEN Germany EU contribution € 1 488 480,00 Address Helmholtzstrasse 10 01069 Dresden See on map Region Sachsen Dresden Dresden, Kreisfreie Stadt Activity type Higher or Secondary Education Establishments Principal investigator Triantafyllos Chavakis (Prof.) Administrative Contact Friederieke Noack (Ms.) Links Contact the organisation Opens in new window Website Opens in new window Other funding No data
