Senescent endothelial cells promote pathogenic neutrophil trafficking in inflamed tissues.

Cellular senescence is a hallmark of advanced age and a major instigator of numerous inflammatory pathologies. While endothelial cell (EC) senescence is aligned with defective vascular functionality, its impact on fundamental inflammatory responses in vivo at single-cell level remain unclear. To directly investigate the role of EC senescence on dynamics of neutrophil-venular wall interactions, we applied high resolution confocal intravital microscopy to inflamed tissues of an EC-specific progeroid mouse model, characterized by profound indicators of EC senescence.

Effect of cytokine-induced alterations in extracellular matrix composition on diabetic retinopathy-relevant endothelial cell behaviors.

Retinal vascular basement membrane (BM) thickening is an early structural abnormality of diabetic retinopathy (DR). Recent studies suggest that BM thickening contributes to the DR pathological cascade; however, much remains to be elucidated about the exact mechanisms by which BM thickening develops and subsequently drives other pathogenic events in DR. Therefore, we undertook a systematic analysis to understand how human retinal microvascular endothelial cells (hRMEC) and human retinal pericytes (hRP) change their expression of key extracellular matrix (ECM) constituents when treated with diabetes-relevant stimuli designed to model the three major insults of the diabetic environment: hyperglycemia, dyslipidemia, and inflammation.

Nuclear factor of activated T-cells (NFAT) regulation of IL-1β-induced retinal vascular inflammation.

Chronic low-grade retinal inflammation is an essential contributor to the pathogenesis of diabetic retinopathy (DR). It is characterized by increased retinal cell expression and secretion of a variety of inflammatory cytokines; among these, IL-1β has the reputation of being a major driver of cytokine-induced inflammation. IL-1β and other cytokines drive inflammatory changes that cause damage to retinal cells, leading to the hallmark vascular lesions of DR; these include increased leukocyte adherence, vascular permeability, and capillary cell death.

Palmitic Acid Induces Müller Cell Inflammation that is Potentiated by Co-treatment with Glucose.

Chronic hyperglycemia is thought to be the major stimulator of retinal dysfunction in diabetic retinopathy (DR). Thus, many diabetes-related systemic factors have been overlooked as inducers of DR pathology. Cell culture models of retinal cell types are frequently used to mechanistically study DR, but appropriate stimulators of DR-like factors are difficult to identify.