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