Cornea · 2013
Tissue microarray analysis of cyclin-dependent kinase inhibitors p21 and p16 in Fuchs dystrophy.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
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Matthaei Mario, Lackner Eva-Maria, Meng Huan, Hicks Jessica L, Meeker Alan K, Eberhart Charles G, Jun Albert S
Аннотация
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.
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.