May 2003
Volume 44, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2003
RPE Express MT1-MMP and its Levels Are Regulated by Estrogen and Oxidant Injury
Author Affiliations & Notes
  • S. Elliot
    Medicine, University of Miami, Miami, FL, United States
  • P. Catanuto
    Ophthalmology, Bascom Palmer, Miami, FL, United States
  • M.E. Marin-Castaño
    Ophthalmology, Bascom Palmer, Miami, FL, United States
  • S. Pereira-Simon
    Ophthalmology, Bascom Palmer, Miami, FL, United States
  • S.W. Cousins
    Ophthalmology, Bascom Palmer, Miami, FL, United States
  • Footnotes
    Commercial Relationships  S. Elliot, None; P. Catanuto, None; M.E. Marin-Castaño, None; S. Pereira-Simon, None; S.W. Cousins, None.
Investigative Ophthalmology & Visual Science May 2003, Vol.44, 478. doi:https://doi.org/
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      S. Elliot, P. Catanuto, M.E. Marin-Castaño, S. Pereira-Simon, S.W. Cousins; RPE Express MT1-MMP and its Levels Are Regulated by Estrogen and Oxidant Injury . Invest. Ophthalmol. Vis. Sci. 2003;44(13):478. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Abstract: : Purpose: Age-related macular degeneration (ARMD) is the most important cause of lost central vision in the elderly. Oxidant injury to the RPE has been implicated as a mechanism for the development of subRPE deposits and drusen in ARMD. Our previous data indicated that RPE express high levels of proMMP-2 and active MMP-2, and that the levels are regulated by estrogen. Following RPE oxidant injury, active MMP-2 declines but proMMP-2 increases. Since MT1-MMP is one of the key cell surface enzymes involved in activation of proMMP-2, we investigated whether MT1-MMP was expressed in RPE cells, if it was regulated by estrogen and if the levels of expression changed after oxidant injury as a mechanism for changes in MMP-2 activation. Methods: Confluent cultures of the human RPE-19 cell line were incubated in phenol red free medium containing 0.1% fetal bovine serum with and without 17ß-estradiol treatment. ARPE-19 cells oxidant injured after transient exposure to H2O2 and MPO were collected for protein. 100ug of protein extract was immunoprecipitated and western analysis performed for MMP-2 and MT1-MMP. Zymography for MMP-2 was also performed. Results: Western blotting indicated that abundant MT1-MMP protein was expressed in RPE-19 cells and cell membranes. After oxidant injury, active MMP-2 expression decreased. In contrast, injury increased MT1-MMP. Interestingly, treatment with 17ß-estradiol prevented the injury induced increase in MT1-MMP expression. Conclusions: RPE express the cell surface protease MT1-MMP, and its levels are regulated by estrogen and oxidant injury. Changes in MT1-MMP protein expression may be associated with dysregulation activation of proMMP-2 and other matrix molecules following oxidant injury, and treatment with 17ß-estradiol may prevent this effect.

Keywords: age-related macular degeneration • oxidation/oxidative or free radical damage • retinal pigment epithelium 
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