@article {283991,
	title = {Notch signaling functions in retinal pericyte survival},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {55},
	number = {8},
	year = {2014},
	month = {2014 Jul 11},
	pages = {5191-9},
	abstract = {PURPOSE: Pericytes, the vascular cells that constitute the outer layer of capillaries, have been shown to have a crucial role in vascular development and stability. Loss of pericytes precedes endothelial cell dysfunction and vascular degeneration in small-vessel diseases, including diabetic retinopathy. Despite their clinical relevance, the cellular pathways controlling survival of retinal pericytes remain largely uncharacterized. Therefore, we investigated the role of Notch signaling, a master regulator of cell fate decisions, in retinal pericyte survival. METHODS: A coculture system of ligand-dependent Notch signaling was developed using primary cultured retinal pericytes and a mesenchymal cell line derived from an inducible mouse model expressing the Delta-like 1 Notch ligand. This model was used to examine the effect of Notch activity on pericyte survival using quantitative PCR (qPCR) and a light-induced cell death assay. The effect of Notch gain- and loss-of-function was analyzed in monocultures of retinal pericytes using antibody arrays to interrogate the expression of apoptosis-related proteins. RESULTS: Primary cultured retinal pericytes differentially expressed key molecules of the Notch pathway and displayed strong expression of canonical Notch/RBPJK (recombination signal-binding protein 1 for J-kappa) downstream targets. A gene expression screen using gain- and loss-of-function approaches identified genes relevant to cell survival as downstream targets of Notch activity in retinal pericytes. Ligand-mediated Notch activity protected retinal pericytes from light-induced cell death. CONCLUSIONS: Our results have identified signature genes downstream of Notch activity in retinal pericytes and suggest that tight regulation of Notch signaling is crucial for pericyte survival.},
	keywords = {Animals, Cattle, Cell Survival, Coculture Techniques, Mesenchymal Stromal Cells, Models, Animal, Pericytes, Polymerase Chain Reaction, Proto-Oncogene Proteins, Receptors, Notch, Retina, Signal Transduction},
	issn = {1552-5783},
	doi = {10.1167/iovs.14-14046},
	author = {Arboleda-Velasquez, Joseph F and Primo, Vincent and Graham, Mark and James, Alexandra and Manent, Jan and D{\textquoteright}Amore, Patricia A}
}
