December 2002
Volume 43, Issue 13
Free
ARVO Annual Meeting Abstract  |   December 2002
Non-Feminizing Estrogen Analogs are Effective Neuroprotectants Against Glutamate Induced Cytotoxicity of Retinal Ganglion Cells
Author Affiliations & Notes
  • N Agarwal
    Pathology and Anatomy
    UNT Health Science Center Ft Worth TX
  • N Patel
    Pathology and Anatomy
    UNT Health Science Center Ft Worth TX
  • ZY Cai
    Pharmacology Washington University School of Medicine St Louis MO
  • D Covey
    Pharmacology Washington University School of Medicine St Louis MO
  • JW Simpkins
    Pharmacology and Neuroscience
    UNT Health Science Center Ft Worth TX
  • Footnotes
    Commercial Relationships   N. Agarwal, None; N. Patel, None; Z.Y. Cai, None; D. Covey, None; J.W. Simpkins, None. Grant Identification: American Health Assistance Foundation-National Glaucoma Program; Alcon Research, Ltd
Investigative Ophthalmology & Visual Science December 2002, Vol.43, 2200. doi:
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    • Get Citation

      N Agarwal, N Patel, ZY Cai, D Covey, JW Simpkins; Non-Feminizing Estrogen Analogs are Effective Neuroprotectants Against Glutamate Induced Cytotoxicity of Retinal Ganglion Cells . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2200.

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

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Abstract

Abstract: : Purpose: The non-feminizing estrogen analogs have been shown to be effective and potent neuroprotectants in a number of insults both in vivo and in vitro. In our studies we explored the efficacy of three estrogen analogs (ZYC-1m, 3, and 10) that we have shown to be effective against insults in neuronal cultures for their ability to protect rat retinal ganglion cells against glutamate cytotoxicity as an in vitro model of glaucoma. Methods: Transformed rat RGC (RGC-5 cells) (Mol Brain Res, 2001) were plated in 24-well plates with various concentrations of ZYC-1, 3, and 10 and 24 hours later the cells were exposed to glutamic acid (5 mM). Cell viability was determined 24 hours after glutamate exposure. The expression of estrogen receptors α and ß was determined by RT-PCR and immunocytochemistry using specific antibodies and primers. Results: A 24-hour glutamate exposure resulted in about 50% cell death. The three non-feminizing estrogens protected the RGC-5 cells, in a dose dependent manner, from glutamate toxicity. The potency of the protection was in the order of ZYC-1≷ZYC-3≷ZYC-10. The neuroprotective concentrations of all compounds ranged from about 1 µM to 3 µM. The antagonist of α and ß estrogen receptor, ICI compound, did not inhibit the neuroprotecting activity of the analogs. The RGC-5 cells were shown to express both α and ß estrogen receptors by RT-PCR and immunocytochemistry. Conclusion: These results demonstrate that non-feminizing estrogen analogs act independent of estrogen receptors and thus may be of therapeutic value in targeting primary retinal pathologies such as glaucoma.

Keywords: 489 neuroprotection • 415 ganglion cells • 341 cell death/apoptosis 
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