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 Keith Meeker, Charles G Eberhart, Albert Jun

Research output: Contribution to journalArticle

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

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Fuchs' Endothelial Dystrophy
Tissue Array Analysis
Cyclin-Dependent Kinase Inhibitor p16
Cyclin-Dependent Kinase Inhibitor p21
Corneal Diseases
Technology
Corneal Endothelium
Keratoconus
Penetrating Keratoplasty
Cell Aging
Paraffin
Cornea
Autopsy
Proteins
Outcome Assessment (Health Care)

Keywords

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

ASJC Scopus subject areas

  • Ophthalmology

Cite this

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 Keith; Eberhart, Charles G; Jun, Albert.

In: Cornea, Vol. 32, No. 4, 04.2013, p. 473-478.

Research output: Contribution to journalArticle

Matthaei, Mario ; Lackner, Eva Maria ; Meng, Huan ; Hicks, Jessica L. ; Meeker, Alan Keith ; Eberhart, Charles G ; Jun, Albert. / Tissue microarray analysis of cyclin-dependent kinase inhibitors p21 and p16 in fuchs dystrophy. In: Cornea. 2013 ; Vol. 32, No. 4. pp. 473-478.
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