July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Localization of CDKN2A/p16 -positive cells in the corneal endothelium of Fuchs dystrophy patients
Author Affiliations & Notes
  • Mario Matthaei
    Dept. of Ophthalmology, University of Cologne, Cologne, Germany
  • Manuel Schmidt
    Dept. of Ophthalmology, University of Cologne, Cologne, Germany
  • Agathe Hribek
    Dept. of Ophthalmology, University of Cologne, Cologne, Germany
  • Sebastian E Siebelmann
    Dept. of Ophthalmology, University of Cologne, Cologne, Germany
  • Björn Bachmann
    Dept. of Ophthalmology, University of Cologne, Cologne, Germany
  • Claus Cursiefen
    Dept. of Ophthalmology, University of Cologne, Cologne, Germany
  • Ludwig M Heindl
    Dept. of Ophthalmology, University of Cologne, Cologne, Germany
  • Footnotes
    Commercial Relationships   Mario Matthaei, None; Manuel Schmidt, None; Agathe Hribek, None; Sebastian Siebelmann, None; Björn Bachmann, None; Claus Cursiefen, None; Ludwig Heindl, None
  • Footnotes
    Support  German Research Foundation (FOR2240 to CC, LMH; MA 5110/5-1 to MM; HE 6743/2-1, HE 6743/3-1, HE 6743/3-2 to LMH; CU 47/6-1, CU 47/9- 1, CU 47/12-1 to CC), FORTUNE Program University of Cologne (to MM and to LMH); GEROK Program University of Cologne (to LMH), EU COST BM1302 "Joining Forces in Corneal Regeneration" (to CC, LMH), Dr. Gabriele Lederle Foundation, Taufkirchen (to LMH), Brigitte and Dr. Konstanze Wegener foundation (to LMH), Marie-Louise Geissler foundation (to LMH), EU Arrest Blindness (to CC).
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 2169. doi:
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    • Get Citation

      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)

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Abstract

Purpose : 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.

Methods : 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).

Results : 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)

Conclusions : 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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