Tissue microarray analysis of cyclin-dependent kinase inhibitors p21 and p16 in fuchs dystrophy

Mario Matthaei, Eva Maria Lackner, Huan Meng, Jessica L. Hicks, Alan K. Meeker, Charles G. Eberhart, Albert S. Jun

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)473-478
Number of pages6
JournalCornea
Volume32
Issue number4
DOIs
StatePublished - Apr 2013

Keywords

  • Fuchs dystrophy
  • cyclin-dependent kinase inhibitor
  • tissue microarray

ASJC Scopus subject areas

  • Ophthalmology

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