May 2006
Volume 47, Issue 13
ARVO Annual Meeting Abstract  |   May 2006
Brimonidine Neuroprotective Effect in a Mouse Model of Ischemic Optic Neuropathy
Author Affiliations & Notes
  • M. Hasanreisoglu
    Ophthalmology, Rabin Medical Center, Petach Tiqwa, Israel
  • B.R. Avraham
    The Krieger Eye Research Laboratory, FMRC, Tel Aviv University, Petach Tiqwa, Israel
    Life Science, Bar Ilan University, Ramat Gan, Israel
  • Y. Cohen
    Sheba Cancer Research Center, Sheba Medical Center, Ramat Gan, Israel
  • D. Weinberger
    Ophthalmology, Rabin Medical Center, Petach Tiqwa, Israel
  • N. Goldenberg–Cohen
    The Krieger Eye Research Laboratory, FMRC, Tel Aviv University, Petach Tiqwa, Israel
  • Footnotes
    Commercial Relationships  M. Hasanreisoglu, None; B.R. Avraham, None; Y. Cohen, None; D. Weinberger, None; N. Goldenberg–Cohen, None.
  • Footnotes
    Support  The Zanvyl and Isabel Krieger Fund, Novartis Ophthalmics
Investigative Ophthalmology & Visual Science May 2006, Vol.47, 4850. doi:
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      M. Hasanreisoglu, B.R. Avraham, Y. Cohen, D. Weinberger, N. Goldenberg–Cohen; Brimonidine Neuroprotective Effect in a Mouse Model of Ischemic Optic Neuropathy . Invest. Ophthalmol. Vis. Sci. 2006;47(13):4850.

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

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Purpose: : To elucidate the potential protective effect of brimonidine following induction of ischemic optic neuropathy in a mouse model (rAION).

Methods: : Anterior ischemic optic neuropathy was induced in C57B1/6 mice by localized illumination of a photosensitive RB agent at 12, 24, or 48 hours following intraperitoneal (IP) injection of a single dose of brimonidine or 3 days of treatment with topical brimonidine 2% eyedrops. The animals were euthanized on day 1, 3, or 21 after injury for tissue staining and RT–PCR analysis of ischemia–, angiogenesis–, and oxidative–stress–induced gene expression. Findings were compared with untreated rAION eyes and with the contralateral healthy eyes of the treated mice.

Results: : In the untreated rAION–induced eyes, at day 1 following rAION induction, levels of endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF), glutathione peroxidase–1 (Gpx), copper–zinc superoxide dismutase–1 (SOD1), hypoxia inducible factor 1, alpha subunit (HIF–1 alpha) and pigment epithelium derived factor (PEDF) were reduced to 45%, 80%, 80%, 80%, 89% and 90% of levels in healthy control eyes. Heme–oxygenase–1 (HO–1) levels did not change. On day 3, eNOS, PEDF, and Gpx returned to normal levels, but VEGF, HO–1, and SOD1 increased 1.2–, 1.4–, and 1.5–fold, respectively. On day 21 following AION induction, the levels of expression of all genes returned to normal, except for HO–1 and, to a lesser extent, PEDF, which were high. By contrast, in eyes treated with bromonidine, there was no change in PEDF, and HO–1 increased, but to a lesser extent. This effect was true for both modes of treatment, but more significant for the IP route. Topical treatment was also associated with reduced levels of VEGF, Tie2, HIF–1–alpha, Gpx, and SOD1. Interestingly, IP treatment had an inverse effect on VEGF and Tie2 at 21 days.

Conclusions: : Brimonidine treatment causes changes in the level of expression of various ischemia–, oxidative–stress–, and angiogenesis–induced genes following AION induction. The neuroprotective effect of these changes will be discussed and the preferred route of administration evaluated. These results are in agreement with previously published data, and should be further applied to patients diagnosed with AION in the acute phase.

Keywords: neuroprotection • ischemia 

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