Regulation of matrix metalloproteinase expression by tumor necrosis factor in a murine model of retinal neovascularization.

摘要: Purpose Hypoxia and growth factors are postulated to be involved in the development of retinal neovascularization through regulation extracellular proteinase production. It has been shown that matrix metalloproteinases (MMPs) elevated retina during process. However, mechanisms regulate expression these enzymes not well characterized. The present study examines potential role tumor necrosis factor (TNF)-alpha as a regulator MMPs Methods C57/Bl6 mice were treated with 75% oxygen (experimental) or room air (control) from postnatal days (P)7 P12, followed by until P17. Retinas collected at P13, P15, P17 total RNA analyzed for relative level TNFalpha, TNF receptor (p55), TNFalpha-converting enzyme (TACE). Immunostaining was used identify changes protein localize TNFalpha within specific cell types. stimulating microvascular endothelial (RMVEC) production evaluated using isolated murine RMVECs grown normoxic hypoxic conditions. Message RT-PCR zymographic analysis. Results mRNA increased retinas experimental animals on P13 early stages neovascularization. In addition being expressed Muller glial cells inner nuclear layer, additional noted outer layer animals. No significant apoptosis detected Isolated did significantly increase MMP directly response stimulus, but required presence exogenous TNFalpha. MT1-MMP, MMP-3, MMP-9 cells. levels TACE p55, proteins important mediating found angiogenic protein, vascular (VEGF), which also retinas. Conclusions mouse exposed stimuli. Increased does occur stimulus. These responsive, however, stimulation enhances members family. VEGF plays this process its p55 findings support hypothesis two have