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