April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
The effect of periocularly administered candesartan-PLGA microparticles on diabetes-induced retinal inflammatory damage
Author Affiliations & Notes
  • Masanori Fukumoto
    Ophthalmology, Osaka Medical College, Takatsuki, Japan
  • Shinji Takai
    Pharmacology, Osaka Medical College, Takatsuki, Japan
  • Toyofumi Nakanishi
    Clinical and Laboratory Medicine, Osaka Medical College, Takatsuki, Japan
  • Taeko Horie
    Ophthalmology, Osaka Medical College, Takatsuki, Japan
  • Seita Morishita
    Ophthalmology, Osaka Medical College, Takatsuki, Japan
  • Hidehiro Oku
    Ophthalmology, Osaka Medical College, Takatsuki, Japan
  • Tsunehiko Ikeda
    Ophthalmology, Osaka Medical College, Takatsuki, Japan
  • Footnotes
    Commercial Relationships Masanori Fukumoto, None; Shinji Takai, None; Toyofumi Nakanishi, None; Taeko Horie, None; Seita Morishita, None; Hidehiro Oku, None; Tsunehiko Ikeda, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 4924. doi:
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      Masanori Fukumoto, Shinji Takai, Toyofumi Nakanishi, Taeko Horie, Seita Morishita, Hidehiro Oku, Tsunehiko Ikeda; The effect of periocularly administered candesartan-PLGA microparticles on diabetes-induced retinal inflammatory damage. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4924.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: The purpose of current study was to determine whether periocular candesartan, an angiotensinII typeI receptor antagonist, -poly(lactic-co-glycolic acid : PLGA) microparticles alleviate diabetes-induced inflammation in a Sprague Dawley (SD) rats.

Methods: Normal and streptozocin-diabetic male SD rats were divided into three groups: normal, diabetic, diabetic+candesatan. The plasma glucose concentration was assessed by glucose oxidase method. Systolic blood pressure (SBP) was determined by tail-cuff method. The candesartan-PLGA microparticles containing 370ug of candesartan was administered periocularly to one eye (ipsilateral) and PLGA microparticles as vehicle to another eye (contralateral) of diabetic+candesatan group. Leukocyte adhesion to retinal vasculature was evaluated with a concanavalin A lectin perfusion-labelling technique. The alteration of blood retinal barrier permeability was assessed using evans blue technique. Retinal mRNA expression and protein levels of VEGF, intercellular adhesion molecule (ICAM)-1 and monocyte chemotactic protein (MCP)-1 were examined by RT-PCR and Western blot analysis.

Results: No significant difference in the plasma glucose concentration was detected between diabetic and diabetic+candesatan group. No significant difference in SBP was detected between three groups. Treatment with periocularly administered candesartan-PLGA microparticles significantly decreased the permeability of the retinal microvessels. The number of adherent leukocytes was significantly reduced, together with retinal VEGF, ICAM-1 and MCP-1 in the diabetic+candesatan group compared with the diabetic group.

Conclusions: The periocular administration of candesartan-PLGA microparticles inhibit diabetes-induced retinal inflammatory damage, indicating their potential usefulness in treating diabetic retinopathy.

Keywords: 499 diabetic retinopathy • 503 drug toxicity/drug effects  
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