期刊
EXPERIMENTAL EYE RESEARCH
卷 90, 期 1, 页码 10-16出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.exer.2009.09.001
关键词
mouse retinal pigmented ephitelial cells; ERKO mice; estrogen receptors; extracellular matrix
资金
- National Institutes of Health, National Eye Institute [R01 EY1447-04]
- NATIONAL EYE INSTITUTE [R01EY014477, P30EY005722] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES [ZIAES070065] Funding Source: NIH RePORTER
Epidemiological data suggest that estrogen deficiency in postmenopausal women may contribute to the severity of AMD. We discovered that 17 beta-estradiol (E-2) 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)beta 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 ERKO beta mice. In addition RPE isolated from ERKO beta 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 ERKO beta mice. These data suggest that mice which lack ER beta are more susceptible to in vivo injury associated with environmental light and high fat diet. (C) 2009 Elsevier Ltd. All rights reserved.
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