ZnPcS_4-BSA光动力疗法治疗大鼠脉络膜新生血管的研究

Evaluation of the New Photosensitizer ZnPcS_4-BSA for Photodynamic Therapy of the Choroidal Neovascularization in Rats

目的:探讨新型光敏剂ZnPcS_4-BSA(四磺酸酞菁锌与牛血清白蛋白的配合物)介导的光动力疗法对脉络膜新生血管的疗效及应用前景。方法:每只BN大鼠一眼作为实验眼,另一眼作为对照眼,在间接检眼镜下用氩激光光凝视网膜,于光凝后14、21、28天时行眼底光学相干断层扫描(OCT)和荧光血管造影(FFA)等检查。光凝21天后,进行光动力治疗(PDT),照射能量密度为50J/cm^2,PDT1和PDT2两组分别以ZnPcS_4-BSA和ZnPcS_4为光敏剂,于治疗后24小时和7天进行眼底镜,OCT和FFA等检查,检查后作组织病理学光镜和电镜的观察。结果:光凝后14天时,OCT检查见光凝斑视网膜变薄,脉络膜反射被遮蔽,FFA见少量荧光素渗漏,光镜检查见视网膜神经层变薄。光凝21天后,OCT检查见光凝斑视网膜色素上皮(RPE)层和脉络膜毛细血管层反射光带增厚,光凝后21和28天时,FFA检查分别有55%和35%的光斑有点状荧光素渗漏,光镜检查有脉络膜新生血管形成。PDT1和PDT2组治疗后24h FFA检查CNV各有30%和25%被封闭,7天后各有60%和45%,两组间总的有效封闭率有显著性差异。光镜和电镜检查,PDT2组比PDT1组视网膜色素上皮细胞损伤更为严重。结论:ZnPcS_4-BSA介导的光动力治疗一周后能有效地封闭脉络膜新生血管,比用ZnPcS_4介导的光动力治疗效果更好。

Objective： To investigated the ability of ZnPcS4-BSA （Zinc phthalocyanine tetra-sulfonated--bovine serum albumin） to produce photochemical closure of experimental choroidal neovascularization （CNV） in rats. Methods： CNV was created in the fundi of Brown-Norway rats using the argon laser model and documented by fluorescein angiography （FFA） and optical coherence tomography（OCT）. PDT was performed on the CNV and on normal retina and choroid. The rats were divided into groups of PDT1 and PDT2 by the ZnPcS4 BSA and ZnPcS4. Treatment outcomes were assessed by FFA and OCT and confirmed by light and electron microscopy. Result： Seven and fourteen days after laser injury, the OCT demonstrated nervous layer of retina thinning in the photocoagulated zone. Fluorescein angiography didn＇ t find hyperfluorescence. Twenty one days after laser injury, Fluorescein angiography revealed hyperfluoreseence, with later frames of the angiogram demonstrating increased leakage of fluorescein in the photocoagulated zone. The CNV is represented on the OCT as a highly reflective band merging with RPE/choriocapillaris layer obliterating the double band of fibrosis observed; the reflective fibrotic CNV that had merged with the RPE/ehoriocapillaris band as an elevated reflective mound. FFA and OCT indicated that irradiation with 670nm laser light 20 minutes after ZnPcS4-BSA injection produced complete closure of CNV with minimal damage to overlying retina.Histology of light and electron microscopy demonstrated necrosis of CNV endothelial cells with minimal damage to surrounding tissues. Conclusion： ZnPeS4-BSA selectively localizes to ehoriocapillaris and CNV in rats, resulting in occlusion of laser-in- duced CNV with minimal damage to retina tissues. The effect of ZnPcS4-BSA-PDT was better than ZnPcS4-PDT. It is a potential new strategy for the treatment of macular degeneration and other human diseases manifesting CNV.