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Abstract #12234 Published in IGR 7-2
Increased DNA breaks and up-regulation of both G1 and G2 checkpoint genes p21WAF1/CIP1 and 14-3-3σ in circulating leukocytes of glaucoma patients and vasospastic individuals
Moenkemann H; Flammer J; Wunderlich K; Breipohl W; Schild HH; Golubnitschaja OAmino Acids 2005; 28: 199-205
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.
Dr. O. Golubnitschaja, Department of Radiology, Div. of Molec./Exp. Radiology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, Germany
Classification:
2.2 Cornea (Part of: 2 Anatomical structures in glaucoma)
2.6 Aqueous humor dynamics (Part of: 2 Anatomical structures in glaucoma)
9.2.2 Other risk factors for glaucoma (Part of: 9 Clinical forms of glaucomas > 9.2 Primary open angle glaucomas)