Increased mRNA of Matrix Metalloproteinases (MMPs) in Rabbit Following Exposure to Lipid Hydroperoxide (LHP)

Abstract

Abstract: : Purpose: Previous studies have shown that linoleic acid hydroperoxide (LHP) lead to upregulation of activator protein-1 (AP-1) and increased protein synthesis of matrix metalloproteinase (MMP)-9 in rabbit retina. In the present study, we investigated the relationship of MMP-mRNA during LHP induced neovascularization (NV). Methods: LHP (600µg/100µl) was injected into the vitreous of anesthetized adult male New Zealand white rabbits (Angiogenasis 2:93,1998). At 1, 3, 12, 24hr and 4, 7 and 10 days after LHP in injection, retina and retinal pigment epithelium (RPE) were collected by standard techniques. Total RNA were extracted from retina and RPE and their MMP specific mRNA were amplified by RT-PCR. Results: In both retina and RPE, MMP-2 appeared clearly at 12 hr, then increased until 10 days. MMP-9 was also observed initially at 12 hr but remained throughout until 7 days, returning to baseline by 10 days after the LHP exposure. Conclusions: Remodeling of the retinal extra cellular matix is a prerequisite for neovascularization. The present results indicate that LHP can stimulate mRNA synthesis of MMP-2 and -9 in the retina and RPE after intra vitreous injection. This naturally occurring lipid may be relevant in disorders such as diabetic retinopathopathy.

Keywords: retinal neovascularization • oxidation/oxidative or free radical damage • retina