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Mario Matthaei, Manuel Schmidt, Agathe Hribek, Sebastian E Siebelmann, Björn Bachmann, Claus Cursiefen, Ludwig M Heindl; Localization of CDKN2A/p16 -positive cells in the corneal endothelium of Fuchs dystrophy patients. Invest. Ophthalmol. Vis. Sci. 2019;60(9):2169.
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© ARVO (1962-2015); The Authors (2016-present)
Previous studies demonstrate transcriptional and translational up-regulation of senescence-associated cyclin-dependent kinase inhibitor CDKN2A/p16 in the corneal endothelium of Fuchs endothelial corneal dystrophy (FECD) patients suggesting increased cellular senescence of corneal endothelial cells (CECs). The present study aimed to localize p16-immunopositive CECs in the corneal endothelium of FECD patients.
Descemet endothelium complexes (DECs, diameter 8.0 or 9mm) from 7 patients (female to male ratio 2:5; age mean +/- SD 72.6 +/- 7.5 years) undergoing Descemet membrane endothelial keratoplasty (DMEK) at the Department of Ophthalmology, University of Cologne, Cologne, Germany were collected. DECs were fixed in paraformaldehyde, p16 immunofluroescence flatmount staining was performed and analyzed semiquantiatively using a 5-grade (grade 0-4) scoring system. Corneal endothelial expression of p16 was compared in 1x1mm image sections from the corneal center (central 4mm) versus periphery (peripheral >4mm).
Mean density of evaluable corneal endothelial cells +/- SD was 481 +/- 226 cells/mm2 in the corneal center and 695 +/- 475 cells/mm2 in the corneal periphery. Immunofluorescence analysis of the corneal endothelial center disclosed p16 staining grade 4 in 54.0%, grade 3 in 6.3%, grade 2 in 11.1%, grade 1 in 12.7% and grade 0 in 14.3% of sections. Immunofluorescence p16 staining of the corneal endothelial periphery was grade 4 in 9.7%, grade 3 in 13.8%, grade 2 in 31.2%, grade 1 in 18.5% and grade 0 in 18.3% of sections. Increased p16 expression of CECs in images from the corneal endothelial center versus periphery was statistically significant (p<0.05)
Immunolocalization of p16 provides evidence for increased cellular senescence in the central 4mm of FECD endothelium. Selective removal of senescent CECs may contribute to the beneficial outcome of surgical procedures like Descemetorhexis without endothelial keratoplasty (DWEK) in FECD.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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