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P.-S. Chan, R. A. Kowluru; Role of MMP-9 in Inflammation and Apoptosis of Retinal Capillary Cells in Diabetes. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4915.
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Matrix metalloproteinases (MMPs) are proteolytic enzymes that regulate major biological functions including inflammation, tissue repair and cell signaling. This study aims to elucidate the mechanisms by which MMP-9 could contribute to the development of diabetic retinopathy.
Bovine retinal endothelial cells from the 4th to 8th passage were incubated under normal (5mM) or high (20mM) glucose media for 5 days in the absence and presence of a specific MMP-9 inhibitor. Media were collected and cells were harvested at the end of 5 days. The gene expression of retinal MMP-9, interleukin (IL)-1β and tumor necrosis factor (TNF)α was assessed with PCR while the activity of MMP-9 in the media was determined by gelatin zymography. Apoptosis was measured with an ELISA kit.
The transcript for MMP-9 increased by over 40% in cells incubated in 20mM glucose media, and in the same cells MMP-9 activity was elevated by about 20% compared to the cells in 5mM glucose. These glucose-induced elevations were abrogated to the levels comparable to normal by the MMP-9 inhibitor. Incubation with high glucose elevated the gene expression of pro-inflammatory mediators; IL-1β and TNFα by about 50%, and MMP-9 inhibitor prevented the increases in these inflammatory mediators. Apoptosis of retinal endothelial cells that was increased by 20mM glucose was also suppressed to the normal levels by the MMP-9 inhibitor.
Hyperglycemic conditions activate MMP-9 that is capable of stimulating pro-inflammatory mediators and apoptosis of retinal endothelial cells. This suggests that MMP-9 may play a role in the pathogenesis of diabetic retinopathy by accelerating apoptosis of capillary cells via increasing inflammation.
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