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

• Main Authors: Okuda Y, Fukumoto M, Horie T, Oku H, Takai S, Nakanishi T, Matsuzaki K, Tsujimoto H, Ikeda T
• Format: Article
• Language: English
• Published: Dove Medical Press 2018-12-01
• Series: Clinical Ophthalmology
• Subjects: age-related macular degeneration; choroidal neovascularization; renin-angiotensin system; candesartan; macrophage; monocyte chemotactic protein 1; poly(lactic-co-glycolic acid)
• Online Access: https://www.dovepress.com/periocular-injection-of-candesartan-plga-microparticles-inhibits-laser-peer-reviewed-article-OPTH

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)