Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Dec 31:13:87-93.
doi: 10.2147/OPTH.S181110. eCollection 2019.

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

Affiliations

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

Yoshitaka Okuda et al. Clin Ophthalmol. .

Abstract

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; candesartan; choroidal neovascularization; macrophage; monocyte chemotactic protein 1; poly(lactic-co-glycolic acid); renin-angiotensin system.

PubMed Disclaimer

Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Flat mounted choroids from vehicle-treated eye (A) and CAN-treated eyes (5 mg/eye) (B). An arrowhead in (A) indicates lectin-stained CNV tissues. CAN-treated eyes showed a significant decrease in the CNV volume compared with vehicle-treated eyes (C) (n=5 each; *P<0.05). Abbreviations: CAN, candesartan; CNV, choroidal neovascularization.
Figure 2
Figure 2
We immunohistochemically analyzed the infiltration of macrophages (arrowheads) in murine CNV from vehicle-treated eyes (A) and CAN-treated eyes (B). CAN-treated eyes showed a significant decrease in the number of CD68+ macrophages compared with vehicle-treated eyes (C) (n=5 each; **P<0.01). Abbreviations: CAN, candesartan; CNV, choroidal neovascularization.
Figure 3
Figure 3
Quantitative PCR analysis of Mcp-1, Il-1β, and Vegf mRNA expressions in the vehicle-treated eyes and CAN-treated eyes. Notes: Inhibitory effects of CAN on RPE–choroid production of inflammatory and angiogenic molecules. The expressions of all genes were significantly increased in the control and CAN significantly suppressed these increases (Mcp-1 n=8 each, Vegf n=16 each, Il-1β n=16 each; *P<0.05; **P<0.01, two-tailed Student’s t-test). Abbreviations: CAN, candesartan; RPE, retinal pigment epithelium.

References

    1. Bressler NM, Bressler SB, Fine SL. Age-related macular degeneration. Surv Ophthalmol. 1988;32(6):375–413. - PubMed
    1. Ambati J, Fowler BJ. Mechanisms of age-related macular degeneration. Neuron. 2012;75(1):26–39. - PMC - PubMed
    1. Wong WL, Su X, Li X, et al. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. Lancet Glob Health. 2014;2(2):e106–e116. - PubMed
    1. Friedman DS, O’Colmain BJ, Muñoz B, et al. Prevalence of age-related macular degeneration in the United States. Arch Ophthalmol. 2004;122(4):564–572. - PubMed
    1. Sarwar S, Clearfield E, Soliman MK. Aflibercept for neovascular age-related macular degeneration. Cochrane Database Syst Rev. 2016;8(2):CD011346. - PMC - PubMed