Gender and estrogen supplementation increases severity of experimental choroidal neovascularization

Diego G. Espinosa-Heidmann, Maria E. Marin-Castano, Simone Pereira-Simon, Eleut P. Hernandez, Sharon Elliot, Scott W. Cousins

Research output: Contribution to journalArticle

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Abstract

Observational clinical studies suggest that post-menopausal women may be at risk for more severe age-related macular degeneration, and that estrogen loss due to menopause may contribute. We sought to determine the effect of gender and estrogen status on the severity of choroidal neovascularization (CNV) in a mouse model for experimental choroidal neovascularization. Laser-induced CNV was performed in mice with or without estrogen supplementation. At various times, eyes were removed for analysis of severity of CNV lesions or for extraction of choroidal mRNA to evaluate iNOS, TNF-α, MMP-9, and ER-α expression, which are molecules relevant to angiogenic processes. Also, splenic macrophages were analysed for iNOS to determine the effect of estrogen treatment in vitro. Finally, laser-induced CNV was performed in iNOS -/- mice. Our result showed that aged female mice had significantly larger CNV than age-matched males. Ovariectomy in adult mice did not increase severity, but paradoxically estrogen supplementation after ovariectomy did increase CNV severity. More severe CNV were associated with a significant decrease in choroidal iNOS mRNA. Splenic macrophages from estrogen supplemented mice showed a significant increased in TNF-α mRNA expression (eight fold difference compared to the control) but only a mild change in iNOS mRNA levels (2-3 fold difference). In vitro data further showed that nitric oxide production in splenic macrophages at different estrogen levels was not different from controls. Finally, CNV severity was significantly more severe in iNOS -/- mice, compared to iNOS +/+ mice after laser treatment. In conclusion, aged female mice developed more severe CNV than do males. Estrogen replacement seems to increase severity, possibly by suppressing the upregulation of choroidal iNOS and activating macrophages. The putative beneficial or detrimental role of estrogen biology in age-related macular degeneration must be more carefully evaluated and may vary with the stage of age-related macular degeneration (atrophic or neovascular) as well as with the specific target cell type (monocytes vs. endothelial cell or vascular smooth muscle cell).

Original languageEnglish
Pages (from-to)413-423
Number of pages11
JournalExperimental Eye Research
Volume80
Issue number3
DOIs
StatePublished - Mar 1 2005

Fingerprint

Choroidal Neovascularization
Estrogens
Macular Degeneration
Macrophages
Messenger RNA
Lasers
Ovariectomy
Estrogen Replacement Therapy
Menopause
Matrix Metalloproteinases
Vascular Smooth Muscle
Smooth Muscle Myocytes
Observational Studies
Monocytes
Nitric Oxide
Theoretical Models
Up-Regulation
Endothelial Cells

Keywords

  • Age-related macular degeneration (AMD)
  • Animal model
  • Choroidal neovascularisation (CNV)
  • Estrogen
  • iNOS
  • Laser photocoagulation
  • Macrophage activation

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems

Cite this

Espinosa-Heidmann, D. G., Marin-Castano, M. E., Pereira-Simon, S., Hernandez, E. P., Elliot, S., & Cousins, S. W. (2005). Gender and estrogen supplementation increases severity of experimental choroidal neovascularization. Experimental Eye Research, 80(3), 413-423. https://doi.org/10.1016/j.exer.2004.10.008

Gender and estrogen supplementation increases severity of experimental choroidal neovascularization. / Espinosa-Heidmann, Diego G.; Marin-Castano, Maria E.; Pereira-Simon, Simone; Hernandez, Eleut P.; Elliot, Sharon; Cousins, Scott W.

In: Experimental Eye Research, Vol. 80, No. 3, 01.03.2005, p. 413-423.

Research output: Contribution to journalArticle

Espinosa-Heidmann, DG, Marin-Castano, ME, Pereira-Simon, S, Hernandez, EP, Elliot, S & Cousins, SW 2005, 'Gender and estrogen supplementation increases severity of experimental choroidal neovascularization', Experimental Eye Research, vol. 80, no. 3, pp. 413-423. https://doi.org/10.1016/j.exer.2004.10.008
Espinosa-Heidmann, Diego G. ; Marin-Castano, Maria E. ; Pereira-Simon, Simone ; Hernandez, Eleut P. ; Elliot, Sharon ; Cousins, Scott W. / Gender and estrogen supplementation increases severity of experimental choroidal neovascularization. In: Experimental Eye Research. 2005 ; Vol. 80, No. 3. pp. 413-423.
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