Overexpression of hemopexin in the diabetic eye: A new pathogenic candidate for diabetic macular edema

OBJECTIVE-Hemopexin is a well-recognized permeability factor in the kidney, but its potential role in blood-retinal barrier (BRB) breakdown has not been explored. The main aims of this study were as follows: 1) to determine hemopexin expression in the retina and its content in the vitreous fluid from diabetic patients with diabetic macular edema (DME) and nondiabetic patients, 2) to evaluate the effect of hemopexin on BRB permeability, and 3) to determine whether dexamethasone prevents an eventual hemopexin-induced hyperpermeability. RESEARCH DESIGN AND METHODS-Biological material included 1) retinas from 10 diabetic donors with nonproliferative retinopathy and from 10 nondiabetic donors and 2) vitreous fluid from 14 patients with DME and 14 nondiabetic patients. Hemopexin and hemopexin receptormRNA levels weremeasured by quantitative RT-PCR and hemopexin concentrations by ELISA. The effect of hemopexin on permeability in culture was evaluated in human retinal pigment epithelial (ARPE)-19 cells and bovine retinal endothelial cells. The experiments were repeated in the presence of hemopexin-neutralizing antibodies and dexamethasone. RESULTS-A higher expression of hemopexin was detected in the retinal pigment epithelium (RPE) fromdiabetic patients in comparison with nondiabetic control subjects. Intravitreal hemopexin concentration was higher in patients with DME than in nondiabetic subjects. Hemopexin significantly increased permeability in ARPE-19 cells, which was prevented by both hemopexinneutralizing antibodies and dexamethasone. CONCLUSIONS-Hemopexin is overexpressed in the RPE of diabetic patients with DME and induces the breakdown of RPE cells in vitro. Dexamethasonewas able to prevent hemopexininduced hyperpermeability. Our results suggest that hemopexin can be considered a new pathogenic candidate for DME. © 2013 by the American Diabetes Association.