Unbound MEDLINE

Neuroprotective effects of nonfeminizing estrogens in retinal photoreceptor neurons.

Abstract

PURPOSE
Retinal diseases such as macular degeneration and glaucoma are disorders that target specific retinal neurons that can ultimately lead to vision loss. Under these conditions and pathologies, retinal neurons can die via apoptosis that may be due to increased oxidative stress. The neuroprotective effects of 17β-estradiol (E2) and three synthetic nonfeminizing estrogen analogs (ZYC-26, ZYC-23, and ZYC-3) were investigated to examine their abilities to protect retinal neurons against glutamate toxicity.
METHODS
Using an in vitro model of glutamate-induced cell death in 661W cells, a mouse cone photoreceptor cell line, shown to express both estrogen receptors (ERs) via immunoblotting, was pretreated with E2 and its analogs and cell viability were assessed.
RESULTS
It was observed that E2 and estrogen analogs, ZYC-26 and ZYC-3, were protective against a 5 mM glutamate insult in 661W cells. The neuroprotective abilities of ZYC-26 and ZYC-3 were autonomous of estrogen receptor-α (ERα) and ERβ demonstrated by their ability to protect in the presence of ICI 182780, a pan-ER antagonist with a high affinity for the estrogen receptor. Treatment with PPT and DPN, ERα- and ERβ-specific agonists, respectively, did not protect the 661W cells from the glutamate insult. Studying the membrane ER (mER) or GPR30 did show that activation of the receptor by G1 protected the retinal neuron from insult, whereas G15, an antagonist of the mER was not able to antagonize the protection previously seen.
CONCLUSIONS
These data demonstrate that nonfeminizing estrogens may emerge as useful compounds for neuroprotection of retinal cells.

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  • Publisher Full Text

    • Authors

    Nixon E, Simpkins JW

    Institution

    Department of Pharmacology and Neuroscience, Institute for Aging and Alzheimer's Disease Research, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.

    Source

    Investigative ophthalmology & visual science 53:8 2012 Jul pg 4739-47

    MeSH

    Animals
    Apoptosis
    Cell Line
    Estradiol
    Estradiol Congeners
    Estrogens
    Mice
    Neurons
    Neuroprotective Agents
    Photoreceptor Cells, Vertebrate

    Pub Type(s)

    In Vitro
    Journal Article
    Research Support, U.S. Gov't, Non-P.H.S.

    Language

    eng

    PubMed ID

    22700711