Okuda Yoshitaka, Fukumoto Masanori, Horie Taeko, Oku Hidehiro, Takai Shinji, Nakanishi Toyofumi, Matsuzaki Kaori, Tsujimoto Hiroyuki, Ikeda Tsunehiko
Department of Ophthalmology, Osaka Medical College, Osaka, Japan,
Department of Innovative Medicine, Graduate School of Medicine, Osaka Medical College, Osaka, Japan.
Clin Ophthalmol. 2018 Dec 31;13:87-93. doi: 10.2147/OPTH.S181110. eCollection 2019.
Microparticle technology enables local administration of medication. The purpose of this study was to examine the inhibitory effect of locally administered candesartan (CAN)-encapsulated microparticles on experimental choroidal neovascularization (CNV).
Laser photocoagulation was used to induce CNV in Brown Norway rats. The rats were pretreated with subconjunctival injections of CAN (5.0 mg/eye) or phosphate buffer saline for 3 days before photocoagulation. The volume of CNV was evaluated 7 days after laser injury using the lectin staining technique. The infiltration of macrophages within the CNV lesion was determined using immunofluorescent staining with an anti-CD68 antibody. mRNA levels of MCP-1, IL1-β and VEGF in the retinal pigment epithelium/choroid complex were determined using quantitative PCR (q-PCR).
CNV volume was significantly suppressed by the treatment with CAN compared with that in vehicle-treated eyes (<0.05, two-tailed Student's -test). Subconjunctival injections of CAN decreased the numbers of CD68 cells in the CNV lesion. The increased mRNA levels of MCP-1, IL1-β, and VEGF induced by photocoagulation was significantly suppressed following the local administration of CAN (<0.05, two-tailed Student's -test).
Local administration of CAN inhibited experimentally induced CNV possibly through anti-inflammatory effects.
微粒技术可实现药物的局部给药。本研究的目的是检测局部给予坎地沙坦（CAN）包裹的微粒对实验性脉络膜新生血管（CNV）的抑制作用。
采用激光光凝法在挪威棕色大鼠中诱导CNV。在光凝前3天，对大鼠进行结膜下注射CAN（5.0mg/眼）或磷酸盐缓冲盐水预处理。激光损伤7天后，使用凝集素染色技术评估CNV的体积。使用抗CD68抗体的免疫荧光染色确定CNV病变内巨噬细胞的浸润情况。使用定量PCR（q-PCR）测定视网膜色素上皮/脉络膜复合体中MCP-1、IL1-β和VEGF的mRNA水平。
与载体处理组相比，CAN处理显著抑制了CNV体积（<0.05，双尾Student检验）。结膜下注射CAN减少了CNV病变中CD68细胞的数量。局部给予CAN后，光凝诱导的MCP-1、IL1-β和VEGF的mRNA水平升高受到显著抑制（<0.05，双尾Student检验）。
局部给予CAN可能通过抗炎作用抑制实验性诱导的CNV。
