Blocking hemopexin with specific antibodies: a new strategy for treating diabetic retinopathy

Hemopexin (HPX) is overexpressed in the retina of diabetic patients, and induces the breakdown of the blood-retinal barrier (BRB) in vitro. The present study was aimed at evaluating whether HPX blockade by specific antibodies (aHPX) could avoid vascular leakage in vivo and microvascular angiogenesis in vitro and ex vivo. For this purpose, the effect of intravitreal injections (IVT) of aHPX on vascular leakage was evaluated in db/db mice and rats with streptozotocin-induced diabetes (D-STZ) using the Evans Blue method. Retinal neurodegeneration and inflammation were also evaluated. The antiangiogenic effect of aHPX on human retinal endothelial cells (HREC) was tested by scratch wound healing and tube formation using standardized methods, as well as choroidal sprouting assays from retinal explants obtained in rats. We found that IVT of aHPX significantly reduced vascular leakage, as well as retinal neurodegeneration and inflammation. In addition, treatment with aHPX significantly reduced the HRECs migration and tube formation induced by high glucose concentration, and suppressed choroidal sprouting even after VEGF stimulation, this effect being higher than obtained with Bevacizumab. In conclusion, the anti-permeability and antiangiogenic effects IVT of aHPX suggest the blockade or inhibition of HPX as a new strategy for the treatment of advanced stages of diabetic retinopathy.