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Endothelial homeostasis and dysfunction in metabolic-vascular retina disease: The role of endothelial cell-intrinsic and endothelial cell extrinsic inflammatory pathways

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.

Field of science

  • /medical and health sciences/basic medicine/physiology/homeostasis
  • /medical and health sciences/clinical medicine/endocrinology/diabetes
  • /medical and health sciences/clinical medicine/ophthalmology/retinopathy

Call for proposal

ERC-2011-StG_20101109
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Funding Scheme

ERC-SG - ERC Starting Grant

Host institution

TECHNISCHE UNIVERSITAET DRESDEN
Address
Helmholtzstrasse 10
01069 Dresden
Germany
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 1 488 480
Principal investigator
Triantafyllos Chavakis (Prof.)
Administrative Contact
Friederieke Noack (Ms.)

Beneficiaries (1)

TECHNISCHE UNIVERSITAET DRESDEN
Germany
EU contribution
€ 1 488 480
Address
Helmholtzstrasse 10
01069 Dresden
Activity type
Higher or Secondary Education Establishments
Principal investigator
Triantafyllos Chavakis (Prof.)
Administrative Contact
Friederieke Noack (Ms.)