The effect of ranibizumab versus photodynamic therapy on DNA damage in patients with exudative macular degeneration

[摘要] Purpose: To compare the effect ofranibizumab treatment versus photodynamic therapy (PDT) onsingle-stranded DNA damage in circulating leukocytes in patients withexudative age-related macular degeneration (AMD). Methods: A comparative quantification ofsingle-stranded DNA breaks was performed in circulating leukocytes ofAMD patients before and 30 min, 45 min, 60 min, and 24 h after twodifferent modes of therapy: a) PDT; and b) intravitreal ranibizumabinjection. DNA breaks lead to smaller pieces of DNA, which in anelectrical field, migrate out of the nucleus forming a tail. Damage ofan individual cell was quantified as a comet tail moment. Theproportion of non-zero values compared to the total number ofobservations was referred to as “amount of DNA damage” expressed inarbitrary units (AU). Comparisons between time points and study groupswere assessed using a linear mixed-effect model. Results: PDT induced an increase in theamount of single-stranded DNA damage in the circulating leukocytes from0.2 AU (before treatment) to 0.53 AU (30 min after treatment). Thisincrease was significant (p=0.004). In contrast, after ranibizumabtreatment, the DNA damage in the circulating leukocytes remainedunchanged. Conclusions: PDT purposely induces alocal oxidative stress to damage the newly formed vessels. Our resultsindicate an additional systemic oxidative stress, apparent as amount ofsingle-stranded DNA damage in the circulating leukocytes, for at least30 min after treatment.

[学科分类] 生物化学/生物物理