Abstract
Purpose :
Blood-retinal barrier (BRB) breakdown is a major pathological characteristic of diabetic retinopathy. Erythropoietin (EPO) was protective in diabetic retinopathy. This study was to explore the possible protective mechanisms of EPO on outer BRB in early diabetic rat retinas.
Methods :
Male Sprague-Dawley (SD) rats and ARPE-19 cell line were employed in this study. The SD rats were rendered diabetes with intraperitoneal injection of streptozotocin, followed by Intravitreal injection of EPO 2 hours later; 2 and 4weeks later, the permeability of outer BRB was examined using FITC-dextran leakage assay and the RPE-Bruch’s membrane choriocapillaris complex (RBCC) was isolated for protein detection. The glyoxal-treated ARPE-19 cells were incubated with or without EPO for 3 or 48 hours, and then the cells were studied for cell viability, cell death and permeability of RPE monolayer. The expressions of ZO-1, occludin, E-cadherin, etc. were examined.
Results :
The leakage of FITC-dextran was detected mainly in outer nuclear layer in 2-week diabetic rat retinas and became more obvious in 4-week diabetic rat retinas. The leakage can be largely prevented in EPO-treated diabetic rats. The protein expressions of ZO-1 and occludin in RBCC remained unchanged in 2-week diabetic rats compared with that in normal control, but were decreased significantly in 4-week diabetic rats, which were reversed by EPO treatment. The in vitro study with ARPE-19 cells also confirmed above changes.
Conclusions :
EPO could maintain outer BRB via up-regulating ZO-1 and occludin expressions in diabetic rats. The detailed mechanisms need further exploration.
*Dr. Weiye Li and Dr. Guo-Tong Xu are co-corresponding authors.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.