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Amino Acids

, Volume 28, Issue 2, pp 199–205 | Cite as

Increased DNA breaks and up-regulation of both G1 and G2 checkpoint genes p21WAF1/CIP1 and 14-3-3 σ in circulating leukocytes of glaucoma patients and vasospastic individuals

  • H. Moenkemann
  • J. Flammer
  • K. Wunderlich
  • W. Breipohl
  • H. H. Schild
  • O. Golubnitschaja
Article

Summary.

Objective: Vascular disorder leading to local ischemia/reperfusion has been shown to play an important role in the glaucomatous damage. A decreased expression level of XPGC-gene has been found in circulating leukocytes of normal-tension glaucoma patients. Although decreased activity of XPGC-gene leads to insufficient DNA-repair, no leukopenia has been observed in glaucoma. Molecular mechanisms ensuring cell survival have not been elucidated yet for glaucoma with vascular disorder.

Material and methods: Using the ex vivo optical imaging method of alkaline “comet assay” comparative quantification of DNA breaks was performed in circulating leukocytes of non-glaucomatous non-vasospastic and vasospastic individuals as well as both normal-tension and high-tension glaucoma patients. Relative expression levels of the anti-apoptotic factors P21WAF1/CIP1 and 14-3-3 σ were investigated in all groups tested.

Results and conclusions: The quantification of P21WAF1/CIP1 showed the highest expression rates in high-tension glaucoma patients which were significantly higher than those in all other groups tested. The highest expression rates of 14-3-3 σ were found in both groups of glaucoma patients. These expression levels correlated well with DNA breaks measured. Since the expression of P21WAF1/CIP1 in leukocytes was shown to be crucial for their survival under stress conditions, we suppose further that the up-regulation of this gene is the key event in the survival mechanisms of leukocytes in glaucoma accompanied with vascular disorder. The p21WAF1/CIP1 gene should be further taken into consideration as a potential marker, the up-regulation of which in circulating leukocytes of vasospastic individuals may indicate an increased risk for the developing glaucoma.

Keywords: Glaucoma – Vascular disorder – Circulating leukocytes – Molecular imaging ex vivo – DNA damage – Survival factors P21WAF1/CIP1 and 14-3-3 σ 

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Copyright information

© Springer-Verlag/Wien 2005

Authors and Affiliations

  • H. Moenkemann
    • 1
  • J. Flammer
    • 2
  • K. Wunderlich
    • 2
  • W. Breipohl
    • 3
  • H. H. Schild
    • 1
  • O. Golubnitschaja
    • 1
  1. 1.Department of RadiologyFriedrich-Wilhelms-University of BonnBonnGermany
  2. 2.Ophthalmological Hospital, University of BaselBaselSwitzerland
  3. 3.Department of OphthalmologyFriedrich-Wilhelms-University of BonnBonnGermany

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