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

Mozaffarieh M, Schötzau A, Josifova T, Flammer J - Mol. Vis. (2009)

Bottom Line: DNA breaks lead to smaller pieces of DNA, which in an electrical field, migrate out of the nucleus forming a tail.Comparisons between time points and study groups were assessed using a linear mixed-effect model.This increase was significant (p=0.004).

View Article: PubMed Central - PubMed

Affiliation: University Eye Clinic, Basel, Switzerland.

ABSTRACT

Purpose: To compare the effect of ranibizumab treatment versus photodynamic therapy (PDT) on single-stranded DNA damage in circulating leukocytes in patients with exudative age-related macular degeneration (AMD).

Methods: A comparative quantification of single-stranded DNA breaks was performed in circulating leukocytes of AMD patients before and 30 min, 45 min, 60 min, and 24 h after two different modes of therapy: a) PDT; and b) intravitreal ranibizumab injection. DNA breaks lead to smaller pieces of DNA, which in an electrical field, migrate out of the nucleus forming a tail. Damage of an individual cell was quantified as a comet tail moment. The proportion of non-zero values compared to the total number of observations was referred to as "amount of DNA damage" expressed in arbitrary units (AU). Comparisons between time points and study groups were assessed using a linear mixed-effect model.

Results: PDT induced an increase in the amount of single-stranded DNA damage in the circulating leukocytes from 0.2 AU (before treatment) to 0.53 AU (30 min after treatment). This increase was significant (p=0.004). In contrast, after ranibizumab treatment, the DNA damage in the circulating leukocytes remained unchanged.

Conclusions: PDT purposely induces a local oxidative stress to damage the newly formed vessels. Our results indicate an additional systemic oxidative stress, apparent as amount of single-stranded DNA damage in the circulating leukocytes, for at least 30 min after treatment.

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Related in: MedlinePlus

Amount of DNA damage before and after PDT and ranibizumab treatment. With the exception of columns marked pre, all times are post treatment. PDT induced an increase in the amount of single stranded DNA damage in the circulating leukocytes from 0.22AU (before treatment) to 0.53 AU (30 min after treatment).
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f2: Amount of DNA damage before and after PDT and ranibizumab treatment. With the exception of columns marked pre, all times are post treatment. PDT induced an increase in the amount of single stranded DNA damage in the circulating leukocytes from 0.22AU (before treatment) to 0.53 AU (30 min after treatment).

Mentions: To explore the effect of time for PDT and ranibizumab, we performed a linear mixed-effect model with fixed factor “time” and random factor “subject” on the log-transformed proportions. This model allowed comparisons before treatment with postoperative treatment at the various times of 30 min, 45 min, 60 min, and 24 h. Descriptive statistics and corresponding box plots are reported in Table 2 and Figure 2. A p-value <0.05 was considered significant. The p-values of the statistical tests were interpreted in a purely exploratory manner and were not adjusted for multiple comparisons. All analyses were done using the statistical software R, version 7.1.


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

Mozaffarieh M, Schötzau A, Josifova T, Flammer J - Mol. Vis. (2009)

Amount of DNA damage before and after PDT and ranibizumab treatment. With the exception of columns marked pre, all times are post treatment. PDT induced an increase in the amount of single stranded DNA damage in the circulating leukocytes from 0.22AU (before treatment) to 0.53 AU (30 min after treatment).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2697459&req=5

f2: Amount of DNA damage before and after PDT and ranibizumab treatment. With the exception of columns marked pre, all times are post treatment. PDT induced an increase in the amount of single stranded DNA damage in the circulating leukocytes from 0.22AU (before treatment) to 0.53 AU (30 min after treatment).
Mentions: To explore the effect of time for PDT and ranibizumab, we performed a linear mixed-effect model with fixed factor “time” and random factor “subject” on the log-transformed proportions. This model allowed comparisons before treatment with postoperative treatment at the various times of 30 min, 45 min, 60 min, and 24 h. Descriptive statistics and corresponding box plots are reported in Table 2 and Figure 2. A p-value <0.05 was considered significant. The p-values of the statistical tests were interpreted in a purely exploratory manner and were not adjusted for multiple comparisons. All analyses were done using the statistical software R, version 7.1.

Bottom Line: DNA breaks lead to smaller pieces of DNA, which in an electrical field, migrate out of the nucleus forming a tail.Comparisons between time points and study groups were assessed using a linear mixed-effect model.This increase was significant (p=0.004).

View Article: PubMed Central - PubMed

Affiliation: University Eye Clinic, Basel, Switzerland.

ABSTRACT

Purpose: To compare the effect of ranibizumab treatment versus photodynamic therapy (PDT) on single-stranded DNA damage in circulating leukocytes in patients with exudative age-related macular degeneration (AMD).

Methods: A comparative quantification of single-stranded DNA breaks was performed in circulating leukocytes of AMD patients before and 30 min, 45 min, 60 min, and 24 h after two different modes of therapy: a) PDT; and b) intravitreal ranibizumab injection. DNA breaks lead to smaller pieces of DNA, which in an electrical field, migrate out of the nucleus forming a tail. Damage of an individual cell was quantified as a comet tail moment. The proportion of non-zero values compared to the total number of observations was referred to as "amount of DNA damage" expressed in arbitrary units (AU). Comparisons between time points and study groups were assessed using a linear mixed-effect model.

Results: PDT induced an increase in the amount of single-stranded DNA damage in the circulating leukocytes from 0.2 AU (before treatment) to 0.53 AU (30 min after treatment). This increase was significant (p=0.004). In contrast, after ranibizumab treatment, the DNA damage in the circulating leukocytes remained unchanged.

Conclusions: PDT purposely induces a local oxidative stress to damage the newly formed vessels. Our results indicate an additional systemic oxidative stress, apparent as amount of single-stranded DNA damage in the circulating leukocytes, for at least 30 min after treatment.

Show MeSH
Related in: MedlinePlus