TY - JOUR
T1 - Differential E-selectin expression by iris versus retina microvascular endothelial cells cultured from the same individuals
AU - Silverman, Matthew D.
AU - Babra, Bobby
AU - Pan, Yuzhen
AU - Planck, Stephen R.
AU - Rosenbaum, James T.
N1 - Funding Information:
We thank the late Paul V. Texeira for his expert technical inputs. This study was supported by NEI Training Grant T32EY07123 to MDS, NEI Grant EY06484 (to JTR/SRP), NEI Grant EY013909 (to Justine Smith and JTR), NIH Core Grant P30EY10572, from unrestricted funds from Research to Prevent Blindness (RPB), the Rosenfeld Family Trust, and from a Tartar Trust Foundation Grant to MDS. JTR is a senior scholar of RPB, and SRP is a scholar of RPB.
PY - 2005/7
Y1 - 2005/7
N2 - The microvasculature of the eye plays a critical role in many ophthalmic diseases, including diabetic retinopathy and macular degeneration. Transcriptional profiling by gene array allows characterization of endothelial cells (EC) and can test for inherent EC diversity relative to the tissue source of the EC. Here, we established highly purified microvascular EC cultures from donor-matched human irises and retinae (4 donor pairs). We used nylon-based gene array kits to compare gene expression in paired confluent EC monolayers, under both quiescent and inflammatory agent (bacterial lipopolysaccharide, LPS; or tumor necrosis-factor alpha, TNFα)-activated conditions. In the absence of an inflammatory agent, iris and retinal ECs from the same donor were remarkably similar in overall gene expression profiles, except for possible differences in the expression of platelet-derived growth factor-A and a DNA mismatch repair protein (mutL homologue). Several detectable transcripts had never previously been reported in the eye. After inflammatory stimulation, significantly greater expression of the adhesion molecule E-selectin mRNA was consistently detected in retinal versus iris EC, and this difference was maintained at the protein level both in cell-surface-expressed and secreted soluble E-selectin protein in paired cultures. Thus, cultured EC derived from adjacent microvascular beds are biologically distinct. Such endothelial diversity could play a role in the pathogenesis of tissue-specific inflammation, infection, neovascularization, and malignancy.
AB - The microvasculature of the eye plays a critical role in many ophthalmic diseases, including diabetic retinopathy and macular degeneration. Transcriptional profiling by gene array allows characterization of endothelial cells (EC) and can test for inherent EC diversity relative to the tissue source of the EC. Here, we established highly purified microvascular EC cultures from donor-matched human irises and retinae (4 donor pairs). We used nylon-based gene array kits to compare gene expression in paired confluent EC monolayers, under both quiescent and inflammatory agent (bacterial lipopolysaccharide, LPS; or tumor necrosis-factor alpha, TNFα)-activated conditions. In the absence of an inflammatory agent, iris and retinal ECs from the same donor were remarkably similar in overall gene expression profiles, except for possible differences in the expression of platelet-derived growth factor-A and a DNA mismatch repair protein (mutL homologue). Several detectable transcripts had never previously been reported in the eye. After inflammatory stimulation, significantly greater expression of the adhesion molecule E-selectin mRNA was consistently detected in retinal versus iris EC, and this difference was maintained at the protein level both in cell-surface-expressed and secreted soluble E-selectin protein in paired cultures. Thus, cultured EC derived from adjacent microvascular beds are biologically distinct. Such endothelial diversity could play a role in the pathogenesis of tissue-specific inflammation, infection, neovascularization, and malignancy.
KW - Cell adhesion molecule
KW - Chemokine
KW - E-selectin
KW - Endothelium
KW - Expression profiling
KW - Heterogeneity
KW - Microcirculation
KW - Ocular inflammation
KW - Tumor necrosis factor-α
KW - cDNA array
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U2 - 10.1016/j.mvr.2005.07.001
DO - 10.1016/j.mvr.2005.07.001
M3 - Article
C2 - 16087199
AN - SCOPUS:27644521906
SN - 0026-2862
VL - 70
SP - 32
EP - 42
JO - Microvascular Research
JF - Microvascular Research
IS - 1-2
ER -