Purchase this article with an account.
P. Catanuto, P. Sanchez, S. Cousins, S. Elliot; Estrogen Receptor β Protects Rpe Cells From Oxidant Injury Induced Ecm Turnover. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4172.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Eyes with age-related macular degeneration (AMD) demonstrate accumulation of specific deposits and extracellular matrix (ECM) molecules under the retinal pigment epithelium (RPE).A substantial body of literature suggests a role for oxidant injury to the RPE as a putative mechanism in the pathogenesis of AMD. We propose that oxidant injury promotes gene expression favoring ECM dysregulation, which is exacerbated in the absence of ERβ. Rho GTPases have been shown to play a role in regulation of ECM although data in RPE cells are incomplete. Stimulation of RhoA activates ERK and NFkB in a tissue and cell type specific manner. Therefore we evaluated whether oxidant injury triggered a series of events starting with RhoA activation leading to a decrease in MMP-2 activity.
Confluent cultures of mouse RPE cell lines were oxidant injured by transient exposure to H2O2 and myeloperoxidase. Some wells were also exposed to Fausidil, a specific inhibitor of RhoA, or injury +Fausidil. Cells were collected for pull down assay, Western analysis and zymography
RPE cells isolated from mice lacking ERβ (ERKOβ) and previously exposed to blue light/high fat diet (oxidant injury) have an increased activation of RhoA. Inhibition of Rho A with fausidil, a specific RhoA inhibitor, partiallly protects against the oxidant injury induced MMP-2 activity decrease (Figure 1). In addition, RhoA activation either by oxidant injury or with a specific RhoA activator induces ERK2 (p42). This can also be blocked by Fausidil .
ERβ activation may prevent the oxidant injury induced RhoA activation increase and subsequent ERK activation. These data suggest ERβ activation may aid in protecting against ECM dysregulation
This PDF is available to Subscribers Only