Female Gender, Estrogen Loss, and Sub-RPE Deposit Formation in Aged Mice

Cousins, Scott W.; Marin‐Castaño, Maria E.; Espinosa‐Heidmann, Diego G.; Αλεξανδρίδου, Αναστασία; Striker, Liliane J.; Elliot, Sharon J.

doi:10.1167/iovs.02-0285

Cited by 69 publications

(51 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…We also reported that aged female or ovariectomized estrogen deficient B6 mice were more susceptible to sub-retinal deposits than males most likely due to dysregulation in matrix turnover (Cousins et al, 2003). In addition, in vitro E 2 administration increased human RPE cell MMP-2 activity (Marin-Castano et al, 2003).…”

Section: Discussionmentioning

confidence: 71%

“…As described for ARPE-19 cells this treatment provides a non-lethal injury as assessed by cell number and a viability assay (Marin-Castano et al, 2005) MMP-2 and TIMP-2 Activity RPE cell supernatants were collected and the protein concentration of the corresponding cell layer determined. MMP-2 activity was assessed with 10% zymogram gels (Invitrogen Corp., Carlsbad, CA), and TIMP-2 activity with reverse zymography gels as described previously (Cousins et al, 2003). In addition, MMP-2 and TIMP-2 were measured using the human Biotrak activity assay which recognizes mouse MMP-2 or TIMP-2 respectively and normalized to cell number (Amersham Biosciences, Piscataway, NJ).…”

Section: Oxidant Injurymentioning

confidence: 99%

See 1 more Smart Citation

Subtype specific estrogen receptor action protects against changes in MMP-2 activation in mouse retinal pigmented epithelial cells

Elliot

Catanuto

Fernández

et al. 2008

Experimental Eye Research

Self Cite

View full text Add to dashboard Cite

Eyes with age-related macular degeneration (AMD) demonstrate accumulation of specific deposits and extracellular matrix (ECM) molecules under the retinal pigment epithelium (RPE). AMD is about two times more prevalent in aging postmenopausal women. Therefore we studied whether 17β-estradiol (E 2 ) modulates the expression and activity of the trimolecular complex (MMP-2, TIMP-2 and MMP-14), molecules which are of major importance for ECM turnover in RPE. We used cell lines isolated from estrogen receptor knockout mice (ERKO) to determine which ER (estrogen receptor) subtype was important for ECM regulation in RPE cells.We found that mouse RPE sheets had higher baseline MMP-2 activity in the presence of ERβ. This correlated with higher MMP-2 activity in RPE cell lines isolated from ERKOα mice. Exposure to E 2 increased MMP-2 activity in mouse RPE cell lines. In addition E 2 increased transcriptional activation of the MMP-2 promoter through a functional Sp1 site which required the presence of ERβ, but not ERα. E 2 also maintained levels of pro MMP-2, and MMP-14 and TIMP-2 activity after oxidant injury. Since the direct effects of E 2 on MMP-2 transcriptional activation and the regulation of the trimolecular complex after oxidant induced injury requires ERβ, this receptor subtype may have a role as a potential therapeutic target to prevent changes in activation of MMP-2.

show abstract

Section: Discussionmentioning

confidence: 71%

Section: Oxidant Injurymentioning

confidence: 99%

Subtype specific estrogen receptor action protects against changes in MMP-2 activation in mouse retinal pigmented epithelial cells

Elliot

Catanuto

Fernández

et al. 2008

Experimental Eye Research

Self Cite

View full text Add to dashboard Cite

show abstract

“…194 A lack of oestrogen was shown to be associated with an increase in basal laminar deposits and thickened Bruch's membranes in mice retinae. 197 The authors postulated that oestrogen downregulated matrix metalloproteinase-2, which is 155 or reported by others. 78, 92 The mechanisms for any association between diabetes and ARMD are unknown.…”

Section: Hormonesmentioning

confidence: 81%

Risk Factors for Age-related Macular Degeneration

Berrow¹,

Bartlett²,

Eperjesi³

et al. 2011

European Ophthalmic Review

View full text Add to dashboard Cite

Age-related macular disease (ARMD) is a degenerative disease of the macula, most common over the age of 50 years.1 It is the leading cause of visual loss within western industrialised countries. [2][3][4] The number of blind registrations attributable to the disease increased by 30-40 % between 1950 and 1990 3 and the number of cases each year is continuing to rise 4-6 as these populations have an increasing longevity. Definition of Age-related Macular DiseaseThe international age-related maculopathy group has defined an international classification system for quantifying and defining the different subgroups of ARMD in an attempt to permit easier comparison of research findings between groups.1 Age-related maculopathy (ARM) is a disorder of the macular area most apparent after age 50 and is characterised by the following:• Areas of drusen which are external to the neuroretina and retinal pigment epithelium (RPE). They are soft and distinct or soft and indistinct. Hard drusen are not characteristic of ARM. Drusen are discrete white-yellow spots containing abnormal extracellular lipoprotein deposits that accumulate between the RPE basal lamina and the inner collagenous layer of Bruch's membrane. 7• Hyperpigmentation in the outer retina or choroid with drusen.• Hypopigmentation of the RPE with drusen.This early stage of the condition may not affect vision, but can predispose patients to visual loss (see Figure 1).Later stages of the condition are classified as 'wet' or 'dry' age-related macular degeneration (AMD). These forms of the disease can occur with or without the involvement of new blood vessel growth. If new vessels are not involved (dry AMD), clinical presentation is a sharply defined round or oval area of hypopigmentation where choroidal vessels are more visible than the surrounding area, with a diameter greater than 175 μm 1 (see Figure 2). This is also known as geographic atrophy (GA).The term 'wet AMD', also known as disciform AMD, exudative AMD or neovascular AMD refers to the development of choroidal neovascularisation (see Figure 3) and has numerous manifestations, including:• choroidal neovascularisation (CNV);• RPE detachment(s);• subretinal or sub-RPE neovascular membrane(s);• deposition of scarring, glial tissue or fibrin-like material within the epiretinal, intraretinal, subretinal or sub-RPE layers;• subretinal haemorrhages (without other retinal vascular cause); and• hard exudates (formed from lipid) associated with the above manifestations (without other retinal vascular cause).This article uses the terms ARM, AMD and ARMD as per the international classification system described. Physiology of Age-related Macular DiseaseThe RPE rests on Bruch's membrane and separates the neural retina from the choriocapillaris. The RPE phagocytoses the outer segment discs of the photoreceptors and is a point of metabolite and waste exchange, which is considered crucial to retinal function. 8 The initial signs of ARMD are variations within and below the RPE, seen as alterations in the pigmentation of the ...

show abstract

“…Mouse (Mus musculus) 0.097 (Cousins et al 2003) 0.036 (Cousins et al 2003) −2.7 5 (Belisle et al 1990) 39 (Belisle et al 1990) 7.8 2 (Belisle et al 1990) 13 (Belisle et al 1990) 6.5…”

Section: Between Species Analysismentioning

confidence: 99%

Does the degree of endocrine dyscrasia post-reproduction dictate post-reproductive lifespan? Lessons from semelparous and iteroparous species

et al. 2017

View full text Add to dashboard Cite

Post-reproductive lifespan varies greatly among species; human post-reproductive lifespan comprises~30-50% of their total longevity, while semelparous salmon and dasyurid marsupials post-reproductive lifespan comprises <4% of their total longevity. To examine if the magnitude of hypothalamic-pituitarygonadal (HPG) axis dyscrasia at the time of reproductive senescence determines post-reproductive lifespan, we examined the difference between pre-and postreproductive (1) circulating sex hormones and (2) the ratio of sex steroids to gonadotropins (e.g., 17β-estradiol/follicle-stimulating hormone (FSH)), an index of the dysregulation of the HPG axis and the level of dyotic (death) signaling post-reproduction. Animals with a shorter post-reproductive lifespan (<4% total longevity) had a more marked decline in circulating sex steroids and corresponding elevation in gonadotropins compared to animals with a longer post-reproductive lifespan (30-60% total longevity). In semelparous female salmon of short post-reproductive lifespan (1%), these divergent changes in circulating hormone concentration postreproduction equated to a 711-fold decrease in the ratio of 17β-estradiol/FSH between the reproductive and post-reproductive periods. In contrast, the decrease in the ratio of 17β-estradiol/FSH in iteroparous female mammals with long post-reproductive lifespan was significantly less (1.7-34-fold) post-reproduction. Likewise, in male semelparous salmon, the decrease in the ratio of testosterone/FSH (82-fold) was considerably larger than for iteroparous species (1.3-11-fold). These results suggest that (1) organisms with greater reproductive endocrine dyscrasia more rapidly undergo senescence and die, and (2) the contribution postreproduction by non-gonadal (and perhaps gonadal) tissues to circulating sex hormones dictates postreproductive tissue health and longevity. In this way, reproduction and longevity are coupled, with the degree of non-gonadal tissue hormone production dictating the rate of somatic tissue demise post-reproduction and the differences in post-reproductive lifespans between species.

show abstract

Female Gender, Estrogen Loss, and Sub-RPE Deposit Formation in Aged Mice

Cited by 69 publications

References 37 publications

Subtype specific estrogen receptor action protects against changes in MMP-2 activation in mouse retinal pigmented epithelial cells

Subtype specific estrogen receptor action protects against changes in MMP-2 activation in mouse retinal pigmented epithelial cells

Risk Factors for Age-related Macular Degeneration

Does the degree of endocrine dyscrasia post-reproduction dictate post-reproductive lifespan? Lessons from semelparous and iteroparous species

Contact Info

Product

Resources

About