Abrogation of MMP-9 gene protects against the development of retinopathy in diabetic mice by preventing mitochondrial damage

OBJECTIVE—In the development of diabetic retinopathy, mito-chondrial dysfunction is considered to play an important role in the apoptosis of retinal capillary cells. Diabetes activates matrix metalloproteinase-9 (MMP-9) in the retina and its capillary cells, and activated MMP-9 becomes proapoptotic. The objective of this study is to elucidate the plausible mechanism by which active MMP-9 contributes to the mitochondrial dysfunction in the retina. RESEARCH DESIGN AND METHODS—Using MMP-9 gene knockout (MMP-KO) mice, we investigated the effect of MMP-9 regulation on diabetes-induced increased retinal capillary cell apoptosis, development of retinopathy, mitochondrial dysfunc-tion and ultrastructure, and mitochondrial DNA (mtDNA) dam-age. To understand how diabetes increases mitochondrial accumulation of MMP-9, interactions between MMP-9 and chap-erone proteins (heat shock protein [Hsp] 70 and Hsp60) wer