Estrogen receptor β protects against in vivo injury in RPE cells

Sharon J. Elliot, Paola Catanuto, Diego G. Espinosa-Heidmann, Pedro Fernandez, Eleut Hernandez, Peter Saloupis, Kenneth Korach, Michael Karl, Scott W. Cousins

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Epidemiological data suggest that estrogen deficiency in postmenopausal women may contribute to the severity of AMD. We discovered that 17β-estradiol (E2) was a crucial regulator of the severity of extracellular matrix turnover (ECM) dysregulation both in vivo and in vitro. We also found in vitro that the presence of estrogen receptor (ER)β regulates MMP-2 activity. Therefore in an attempt to delineate the role of the ER subtypes, female estrogen receptor knockout (ERKO) mice were fed a high-fat diet, and the eyes were exposed to seven 5-second doses of nonphototoxic levels of blue-green light over 2 weeks. Three months after cessation of blue light treatment, transmission electron microscopy was performed to assess severity of deposits, Bruchs membrane changes, and choriocapillaris endothelial morphology. We found that changes in the trimolecular complex of pro-MMP-2, MMP-14 and TIMP-2 correlated with increased Bruch's membrane thickening or sub-retinal deposit formation (basal laminar deposits) in ERKOβ mice. In addition RPE isolated from ERKOβ mice had an increase in expression of total collagen and a decrease in MMP-2 activity. Finally we found that ERK an intermediate signaling molecule in the MMP pathway was activated in RPE isolated from ERKOβ mice. These data suggest that mice which lack ERβ are more susceptible to in vivo injury associated with environmental light and high fat diet.

Original languageEnglish (US)
Pages (from-to)10-16
Number of pages7
JournalExperimental Eye Research
Volume90
Issue number1
DOIs
StatePublished - Jan 1 2010

Keywords

  • ERKO mice
  • estrogen receptors
  • extracellular matrix
  • mouse retinal pigmented ephitelial cells

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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  • Cite this

    Elliot, S. J., Catanuto, P., Espinosa-Heidmann, D. G., Fernandez, P., Hernandez, E., Saloupis, P., Korach, K., Karl, M., & Cousins, S. W. (2010). Estrogen receptor β protects against in vivo injury in RPE cells. Experimental Eye Research, 90(1), 10-16. https://doi.org/10.1016/j.exer.2009.09.001