Clinical Ophthalmology (Dec 2018)

Periocular injection of candesartan-PLGA microparticles inhibits laser-induced experimental choroidal neovascularization

  • Okuda Y,
  • Fukumoto M,
  • Horie T,
  • Oku H,
  • Takai S,
  • Nakanishi T,
  • Matsuzaki K,
  • Tsujimoto H,
  • Ikeda T

Journal volume & issue
Vol. Volume 13
pp. 87 – 93

Abstract

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Yoshitaka Okuda,1 Masanori Fukumoto,1 Taeko Horie,1 Hidehiro Oku,1 Shinji Takai,2 Toyofumi Nakanishi,3 Kaori Matsuzaki,4 Hiroyuki Tsujimoto,4 Tsunehiko Ikeda1 1Department of Ophthalmology, Osaka Medical College, Osaka, Japan; 2Department of Innovative Medicine, Graduate School of Medicine, Osaka Medical College, Osaka, Japan; 3Department of Clinical and Laboratory Medicine, Osaka Medical College, Osaka, Japan; 4Research and Development Division, Hosokawa Micron Corporation, Osaka, Japan Purpose: 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). Methods: 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). Results: CNV volume was significantly suppressed by the treatment with CAN compared with that in vehicle-treated eyes (P<0.05, two-tailed Student’s t-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 (P<0.05, two-tailed Student’s t-test). Conclusion: Local administration of CAN inhibited experimentally induced CNV possibly through anti-inflammatory effects. Keywords: age-related macular degeneration, choroidal neovascularization, renin-angiotensin system, candesartan, macrophage, monocyte chemotactic protein 1, poly(lactic-co-glycolic acid)

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