N-acetylcysteine protects against chorioretinal damage induced by photodynamic therapy for experimental choroidal neovascularization in a rat model

Abstract

We explored the protective effects of N-acetylcysteine (NAC) on chorioretinal damage induced by photodynamic therapy (PDT) in an experimental rat model of choroidal neovascularization (CNV). Experimental CNV was induced by an argon laser in 24 Brown Norway rats 7 days prior to PDT. Commencing 1 day after CNV induction, 0.5 mL of NAC was orally administered daily to the NAC + group (12 rats), and 0.5 mL of normal saline to the NAC- group (12 rats). Diode laser treatment was delivered for 42 s (total energy, 25 J/cm2) to the left eye prior to verteporfin infusion (PDT-) and to the right eye 15-20 min after such infusion (PDT+). Fluorescein angiography was performed just prior to PDT and enucleation to evaluate fluorescein leakage and CNV closure. We compared the CNV thickness, PDT-induced apoptosis [evaluated via terminal dUTP nick-end labeling (TUNEL)], fluorescein angiographic data, and extents of immunohistofluorescent staining for cleaved caspase-3 and superoxide dismutase (SOD) between the two groups. Fourteen days after diode laser treatment, the CNV closure rate was significantly higher in the PDT-treated than the control group. However, the CNV closure rates did not differ significantly between the NAC- and NAC + groups. The TUNEL activity (a measure of PDT-induced apoptosis) of retinal cells was higher in the NAC-/PDT + than the NAC+/PDT + group at 1, 3, 7, and 14 days. The cleaved caspase-3 and SOD levels were higher in the NAC-/PDT + than the NAC+/PDT + group at 3 and 7 days. PDT triggers oxygen radical-induced injury to, and apoptosis in, the retina. NAC may reduce PDT-induced damage to the retina without compromising the therapeutic efficacy of CNV.