May 2004
Volume 45, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2004
Minocycline is neuroprotective in glaucomatous and post optic nerve–transected rat eyes
Author Affiliations & Notes
  • H. Levkovitch–Verbin
    Ophthalmology, The Sam Rothberg Ophthalmic Molecular Biology Lab, Goldschleger Eye Institute, Tel–Aviv University, Tel–Hashomer, Israel
  • Z. Habot–Wilner
    Ophthalmology, The Sam Rothberg Ophthalmic Molecular Biology Lab, Goldschleger Eye Institute, Tel–Aviv University, Tel–Hashomer, Israel
  • M. Kalev–Landoy
    Ophthalmology, The Sam Rothberg Ophthalmic Molecular Biology Lab, Goldschleger Eye Institute, Tel–Aviv University, Tel–Hashomer, Israel
  • S. Melamed
    Ophthalmology, The Sam Rothberg Ophthalmic Molecular Biology Lab, Goldschleger Eye Institute, Tel–Aviv University, Tel–Hashomer, Israel
  • Footnotes
    Commercial Relationships  H. Levkovitch–Verbin, None; Z. Habot–Wilner, None; M. Kalev–Landoy, None; S. Melamed, None.
  • Footnotes
    Support  Claire and Amedee Maratier Institute, Tel–Aviv University
Investigative Ophthalmology & Visual Science May 2004, Vol.45, 1180. doi:
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      H. Levkovitch–Verbin, Z. Habot–Wilner, M. Kalev–Landoy, S. Melamed; Minocycline is neuroprotective in glaucomatous and post optic nerve–transected rat eyes . Invest. Ophthalmol. Vis. Sci. 2004;45(13):1180.

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

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Abstract

Abstract: : Purpose: To evaluate the neuroprotective effect of minocycline on the survival of retinal ganglion cells (RGCs) in glaucomatous and in post optic nerve–transected rat eyes. Minocycline is a second–generation tetracycline with a recognized remarkable neuroprotective effect in models of brain injury. Methods: The neuroprotective effect of intraperitoneal (IP) injections of minocycline was evaluated and compared to saline injections in Wistar rats by means of two models: the translimbal photocoagulation model for glaucoma (n = 45) and optic nerve transection (n = 103). The neuroprotective effect of oral minocycline 25 mg/kg/day was further investigated 1 week after optic nerve transection (n = 26). RGCs were labeled by applying Rhodamine Dextran to the orbital optic nerve. The mechanism of minocycline's neuroprotective effect was investigated using Hoechst staining for apoptosis (n = 44) and immunohistochemistry to the transcription factor c–jun. Minocycline–treated and saline–treated eyes were compared in a masked way at multiple time points after injury. Results: One week after optic nerve transection, the mean number of surviving RGCs was significantly higher after IP injections of minocycline 15 mg/kg/day (27,521 ± 1,900, p = 0.042), minocycline 22 mg/kg/day (33,430 ± 1,233, p = 0.001), and minocycline 45 mg/kg/day (29,449 ± 2,303, p = 0.008) compared to saline (21,548 ± 1,219). Oral minocycline 25 mg/kg was also neuroprotective at 1 week after optic nerve transection (29,070 ± 4,129 RGCs compared to 24,918 ± 4,453 for saline). In the experimental glaucoma model, the mean number of RGCs after 6 weeks was 62,206 ± 5,750 in the minocycline group compared to 52,371 ± 3,837 RGCs in the saline group. Apoptotic RGCs were observed more in the controls (13 ± 3 cells/section) compared to the minocycline–treated group (8 ± 2 cells/section) at 4 and 7 days after optic nerve transection. The transcription factor c–jun was less activated in RGCs from the minocycline–treated eyes compared to the saline–treated ones at 4 days after optic nerve transection, but this difference was not significant at 1 and 2 weeks. Conclusions: Systemic treatment with minocycline appears to significantly enhance the survival of rat RGCs after optic nerve transection and those with experimental glaucoma. Minocycline delayed the apoptosis pathway among RGCs, perhaps through partial inhibition of the MAP–kinase pathway.

Keywords: ganglion cells • neuroprotection • apoptosis/cell death 
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