Tissue microarray analysis of cyclin-dependent kinase inhibitors p21 and p16 in Fuchs dystrophy
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Tissue microarray analysis of cyclin-dependent kinase inhibitors p21 and p16 in Fuchs dystrophy. / Matthaei, Mario; Lackner, Eva-Maria; Meng, Huan; Hicks, Jessica L; Meeker, Alan K; Eberhart, Charles G; Jun, Albert S.
in: CORNEA, Jahrgang 32, Nr. 4, 01.04.2013, S. 473-8.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Tissue microarray analysis of cyclin-dependent kinase inhibitors p21 and p16 in Fuchs dystrophy
AU - Matthaei, Mario
AU - Lackner, Eva-Maria
AU - Meng, Huan
AU - Hicks, Jessica L
AU - Meeker, Alan K
AU - Eberhart, Charles G
AU - Jun, Albert S
PY - 2013/4/1
Y1 - 2013/4/1
N2 - PURPOSE: To investigate the novel application of tissue microarray (TMA) technology to corneal disease and to report altered protein expression of senescence-associated cyclin-dependent kinase inhibitors p21 and p16 in Fuchs endothelial corneal dystrophy (FECD).METHODS: A TMA including 208 cores was generated from paraffin-embedded tissues, including corneal buttons of 50 FECD and 5 keratoconus patients retrieved after penetrating keratoplasty, 10 autopsy globes with nonpathologic corneas, and nonocular control specimens. TMA sections were immunolabeled for p21 and p16 and analyzed using a 9-grade scoring system (0-8). Result validation was performed by immunolabeling of individual whole tissue sections. Corneal endothelial p21 and p16 expression levels in FECD specimens compared with controls served as main outcome measures.RESULTS: TMA immunohistochemical analysis disclosed increased endothelial expression levels of nuclear p21 in FECD specimens (P < 0.05) and an altered endothelial p16 expression pattern. Immunolabeling of whole tissue sections showed statistically significant endothelial overexpression of both proteins (p21 and p16, P < 0.05).CONCLUSIONS: The present study introduces TMA technology as a valuable tool for molecular high-throughput profiling of corneal tissues. It demonstrates p21 and p16 overexpression in the corneal endothelium of genetically undifferentiated FECD patients supporting a role of cellular senescence in the pathogenesis of FECD.
AB - PURPOSE: To investigate the novel application of tissue microarray (TMA) technology to corneal disease and to report altered protein expression of senescence-associated cyclin-dependent kinase inhibitors p21 and p16 in Fuchs endothelial corneal dystrophy (FECD).METHODS: A TMA including 208 cores was generated from paraffin-embedded tissues, including corneal buttons of 50 FECD and 5 keratoconus patients retrieved after penetrating keratoplasty, 10 autopsy globes with nonpathologic corneas, and nonocular control specimens. TMA sections were immunolabeled for p21 and p16 and analyzed using a 9-grade scoring system (0-8). Result validation was performed by immunolabeling of individual whole tissue sections. Corneal endothelial p21 and p16 expression levels in FECD specimens compared with controls served as main outcome measures.RESULTS: TMA immunohistochemical analysis disclosed increased endothelial expression levels of nuclear p21 in FECD specimens (P < 0.05) and an altered endothelial p16 expression pattern. Immunolabeling of whole tissue sections showed statistically significant endothelial overexpression of both proteins (p21 and p16, P < 0.05).CONCLUSIONS: The present study introduces TMA technology as a valuable tool for molecular high-throughput profiling of corneal tissues. It demonstrates p21 and p16 overexpression in the corneal endothelium of genetically undifferentiated FECD patients supporting a role of cellular senescence in the pathogenesis of FECD.
KW - Aged
KW - Cyclin-Dependent Kinase Inhibitor p16
KW - Cyclin-Dependent Kinase Inhibitor p21
KW - Female
KW - Fuchs' Endothelial Dystrophy
KW - Humans
KW - Immunohistochemistry
KW - Male
KW - Middle Aged
KW - Tissue Array Analysis
U2 - 10.1097/ICO.0b013e31826f324e
DO - 10.1097/ICO.0b013e31826f324e
M3 - SCORING: Journal article
C2 - 23132454
VL - 32
SP - 473
EP - 478
JO - CORNEA
JF - CORNEA
SN - 0277-3740
IS - 4
ER -