Department of Ophthalmology, Seoul National University College of Medicine, Seoul, South Korea; Rheumatology Institute and Research for Sensory Organs Institute, Medical Research Center, Seoul National University, Seoul, South Korea; Department of Ophthalmology, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, South Korea.
Department of Ophthalmology, Seoul National University College of Medicine, Seoul, South Korea; Gondduck Seoul Eye Clinic, Seoul, South Korea.
Photodiagnosis Photodyn Ther. 2018 Sep;23:12-17. doi: 10.1016/j.pdpdt.2018.04.006. Epub 2018 Apr 19.
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.
我们在脉络膜新生血管（CNV）的实验性大鼠模型中探讨了 N-乙酰半胱氨酸（NAC）对光动力疗法（PDT）诱导的脉络膜视网膜损伤的保护作用。
通过氩激光在 24 只布朗挪威大鼠中诱导实验性 CNV，在 PDT 前 7 天。从 CNV 诱导后 1 天开始，NAC+组（12 只大鼠）每天口服 0.5ml NAC，NAC-组（12 只大鼠）口服 0.5ml 生理盐水。在脉络膜荧光素血管造影术（FFA）之前，向左眼施打二极管激光 42 秒（总能量 25J/cm2），然后在脉络膜荧光素血管造影术之后 15-20 分钟向右眼施打。在 PDT 前和眼球摘出前进行 FFA，以评估荧光素渗漏和 CNV 闭合。我们比较了两组之间 CNV 厚度、PDT 诱导的细胞凋亡[通过末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记（TUNEL）法评估]、FFA 数据以及免疫荧光染色的 cleaved caspase-3 和超氧化物歧化酶（SOD）水平。
在二极管激光治疗后 14 天，与对照组相比，PDT 治疗组的 CNV 闭合率明显更高。然而，NAC-和 NAC+组之间的 CNV 闭合率没有显著差异。视网膜细胞的 TUNEL 活性（PDT 诱导的细胞凋亡的一种测量方法）在 NAC-/PDT+组中高于 NAC+/PDT+组，在 1、3、7 和 14 天。在 NAC-/PDT+组中，cleaved caspase-3 和 SOD 水平在 3 和 7 天高于 NAC+/PDT+组。
PDT 引发视网膜的氧自由基诱导损伤和细胞凋亡。NAC 可能会降低 PDT 对视网膜的损伤，而不影响 CNV 的治疗效果。
