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小鼠实验性脉络膜新生血管的光动力疗法

Photodynamic therapy of experimental choroidal neovascularization in the mouse.

作者信息

Odergren Anne, Ming Yue, Kvanta Anders

机构信息

Department of Clinical Neuroscience, Section of Ophthalmology and Vision, Karolinska Institutet, St. Eriks Eye Hospital, Stockholm, Sweden.

出版信息

Curr Eye Res. 2006 Sep;31(9):765-74. doi: 10.1080/02713680600865045.

DOI:10.1080/02713680600865045
PMID:16966149
Abstract

PURPOSE

To evaluate the qualitative and quantitative effects of verteporfin photodynamic therapy (PDT) on laser-induced choroidal neovascularization (CNV) in the mouse.

METHODS

PDT was applied to the normal mouse fundus using light doses of 32, 64, and 83 s, and histological analysis of the treated areas was performed. CNV was induced using krypton laser photocoagulation of the fundus, and the CNV lesions were subsequently treated with PDT using light doses of 32, 64, and 83 s. Enucleated eyes were analyzed with light and transmission electron microscopies, and measurements of CNV size were done on histologic sections and on isolectin B4-stained choroidal flat mounts.

RESULTS

PDT induced a light dose-dependent damage to the surrounding neural retina in normal eyes. At a light dose of 32 s, minimal damage was detected in the neural retina, whereas higher light doses caused distortion and disruption of the outer and inner nuclear layers and of the retinal pigment epithelium. When PDT was applied over laser-induced CNV lesions, the relative height of the lesions was significantly reduced (p < 0.05) using all light doses. Transmission electron microscopy 1 day after PDT treatment revealed occlusion of many of the CNV vessels. One week after PDT treatment, the CNV lesions contained patent vessels irrespective of light dose applied. Accordingly, PDT treatment inhibited (p < 0.05) but did not halt CNV lesion growth.

CONCLUSIONS

PDT treatment of laser-induced CNV may create an acute occlusion of neovessels and an inhibition of CNV lesion growth without apparent injury to the surrounding neural retina. However, PDT-treated areas will remain vascularized with continued growth of the CNV lesion, which in turn may explain the often limited effect of PDT in patients with neovascular age-related macular degeneration. Elevating the PDT light dose will not increase the treatment effect substantially but may lead to increased collateral injury.

摘要

目的

评估维替泊芬光动力疗法(PDT)对小鼠激光诱导脉络膜新生血管(CNV)的定性和定量影响。

方法

使用32、64和83秒的光剂量对正常小鼠眼底进行PDT治疗,并对治疗区域进行组织学分析。通过氪激光眼底光凝诱导CNV,随后使用32、64和83秒的光剂量对CNV病变进行PDT治疗。对摘除的眼球进行光镜和透射电镜分析,并在组织学切片和异凝集素B4染色的脉络膜扁平标本上测量CNV大小。

结果

PDT对正常眼睛周围的神经视网膜造成光剂量依赖性损伤。在32秒的光剂量下,神经视网膜中检测到的损伤最小,而较高的光剂量会导致外核层、内核层和视网膜色素上皮的扭曲和破坏。当在激光诱导的CNV病变上应用PDT时,所有光剂量下病变的相对高度均显著降低(p<0.05)。PDT治疗1天后的透射电镜显示许多CNV血管闭塞。PDT治疗1周后,无论应用何种光剂量,CNV病变中均含有开放的血管。因此,PDT治疗可抑制(p<0.05)但不能阻止CNV病变生长。

结论

PDT治疗激光诱导的CNV可能会使新生血管急性闭塞,并抑制CNV病变生长,而不会对周围神经视网膜造成明显损伤。然而,PDT治疗区域会随着CNV病变的持续生长而保持血管化,这反过来可能解释了PDT在新生血管性年龄相关性黄斑变性患者中效果往往有限的原因。提高PDT光剂量不会显著增加治疗效果,但可能会导致附带损伤增加。

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