Although the Hsp60 gene transcript was increased, its abundance in the mitochondria was decreased, and its interaction with MMP2 was increased. High glucose increased MMP2 and decreased connexin 43 in the mitochondria of retinal endothelial cells.
The results were confirmed in retinal mitochondria isolated from diabetic mouse overexpressing MnSOD and in the retinas of normal rats that received intravitreal administration of MMP2. The effect of the regulation of MMP2 on mitochondrial dysfunction and the subcellular localization of the molecular chaperone important for mitochondrial integrity (Hsp60) and gap junction protein connexin 43 were investigated in retinal endothelial cells. The authors sought to elucidate the possible mechanism by which activated MMP2 contributes to mitochondrial dysfunction. Matrix metalloproteinase-2 (MMP2) becomes activated and proapoptotic, and the therapies that inhibit the development of diabetic retinopathy alleviate MMP2 activation. In the pathogenesis of diabetic retinopathy, retinal mitochondria become dysfunctional, their DNA is damaged, and capillary cells undergo accelerated apoptosis.