Sugisaki Kenji, Usui Tomohiko, Nishiyama Nobuhiro, Jang Woo-Dong, Yanagi Yasuo, Yamagami Satoru, Amano Shiro, Kataoka Kazunori
Department of Ophthalmology, Faculty of Medicine, University of Tokyo, Hongo, Bunkyo-ku, Japan
Invest Ophthalmol Vis Sci. 2008 Mar;49(3):894-9. doi: 10.1167/iovs.07-0389.
To investigate the accumulation of new photosensitizers (PSs), dendrimer porphyrin (DP, free DP), and DP encapsulation into polymeric micelles (DP-micelle) and the efficacy of photodynamic therapy (PDT) in an experimental corneal neovascularization model in mice.
Corneal neovascularization was induced by suturing 10-0 nylon 1 mm away from the limbal vessel in C57BL6/J mice. To determine the accumulation of free DP and DP-micelle, 10 mg/kg free DP or DP-micelle was administered by intravenous injection 4 days after suture placement. Mice were killed 1, 4, 24, and 168 hours after the injection of PS. Twenty-four hours after the administration of free DP or DP-micelle, mice were treated with a diode laser of 438-nm wavelength at 10 or 50 J/cm(2). Fluorescein angiography was performed before and 7 days after irradiation, and the area of corneal neovascularization was quantified.
Free DP and DP-micelle accumulated in the neovascularized area 1 hour to 24 hours after administration. Fluorescence of DP was weaker than that of DP-micelle. Neither DP-micelle nor DP could be detected in normal limbal vasculature. In the PDT experiments using PS, mean residual rates of corneal neovascularization were 10.1% in the mice treated with DP-micelle and 21.6% in the mice treated with free DP at 10 J/cm(2) (P < 0.01). At 50 J/cm(2), mean residual rates of corneal neovascularization were 10.6% in the mice treated with DP-micelle and 13.7% in the mice treated with free DP (P > 0.05). Although corneal neovascularization in PDT-treated mice exhibited significant regression compared with the control group, significant energy-related vessel regression with increasing laser energy could not be observed.
PDT with DP-micelle and free DP can provide efficacious treatment of corneal neovascularization.
研究新型光敏剂（PSs）、树枝状卟啉（DP，游离DP）在小鼠实验性角膜新生血管模型中的蓄积情况以及其包裹于聚合物胶束（DP-胶束）中的情况，同时研究光动力疗法（PDT）的疗效。
在C57BL6/J小鼠中，于距角膜缘血管1mm处缝合10-0尼龙线诱导角膜新生血管形成。为确定游离DP和DP-胶束的蓄积情况，在缝线放置4天后通过静脉注射给予10mg/kg游离DP或DP-胶束。在注射PS后1、4、24和168小时处死小鼠。在给予游离DP或DP-胶束24小时后，用波长438nm的二极管激光以10或50J/cm²进行治疗。在照射前和照射后7天进行荧光素血管造影，并对角膜新生血管面积进行定量分析。
游离DP和DP-胶束在给药后1小时至24小时在新生血管区域蓄积。DP的荧光比DP-胶束的荧光弱。在正常角膜缘血管系统中未检测到DP-胶束和DP。在使用PS的PDT实验中，在10J/cm²时，用DP-胶束治疗的小鼠角膜新生血管的平均残留率为10.1%，用游离DP治疗的小鼠为21.6%（P<0.01）。在50J/cm²时，用DP-胶束治疗的小鼠角膜新生血管的平均残留率为10.6%，用游离DP治疗的小鼠为13.7%（P>0.05）。尽管与对照组相比，PDT治疗的小鼠角膜新生血管有显著消退，但未观察到随着激光能量增加而出现的与能量相关的血管显著消退。
用DP-胶束和游离DP进行的PDT可有效治疗角膜新生血管。
