| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 5936719 | The American Journal of Pathology | 2010 | 8 Pages |
Vision loss in diabetic retinopathy is due to macular edema characterized by increased vascular permeability, which involves phosphorylation associated with activation of protein kinase C (PKC) isoforms. Herein, we demonstrated PKC δ inhibition could prevent blood-retinal barrier breakdown in diabetic retinopathy. Increased vascular permeability of diabetic retina was accompanied by a decrease of zonula occludens (ZO)-1 and ZO-2 expression. In diabetic retina and advanced glycation end product-treated human retinal microvascular endothelial cells, vascular leakage and loss of ZO-1 and ZO-2 on retinal vessels were effectively restored or prevented with treatment of rottlerin, transfection of PKC-δ-DN, or siRNA for PKC δ. Interestingly, PKC δ translocated from cytosol to membrane in advanced glycation end product-treated human retinal microvascular endothelial cells, which was blocked by PKC δ inhibition. Taken together, PKC δ activation, related to its subcellular translocation, is involved in vascular permeability in response to diabetes, and inhibition of PKC δ effectively restores loss of tight junction proteins in retinal vessels. Therefore, we suggest that inhibition of PKC δ could be an alternative treatment to blood-retinal barrier breakdown in diabetic retinopathy.
