RGC death in mice after optic nerve crush injury: Oxidative stress and neuroprotection

H. Levkovitch-Verbin, C. Harris-Cerruti, Y. Groner, L. A. Wheeler, M. Schwartz*, E. Yoles

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

167 Scopus citations

Abstract

PURPOSE. To establish a method for morphometric analysis of retrogradely labeled retinal ganglion cells (RGCs) of the mouse retina, to be used for the study of molecular aspects of RGC survival and neuroprotection in this model; to evaluate the effect of overexpression of Cu-Zn-superoxide dismutase (CuZnSOD) on RGC survival after severe crush injury to the optic nerve, and to assess the effect of the α2-adrenoreceptor agonist brimonidine, recently shown to be neuroprotective, on RGC survival. METHODS. A severe crush injury was inflicted unilaterally in the orbital portion of the optic nerves of wild-type and transgenic (Tg-SOD) mice expressing three to four times more human CuZnSOD than the wild type. In each mouse all RGCs were labeled 72 hours before crush injury by stereotactic injection of the neurotracer dye FluoroGold (Fluorochrome, Denver, CO) into the superior colliculus. Survival of RGCs was then assessed morphometrically, with and without systemic injection of brimonidine. RESULTS. Two weeks after crush injury, the number of surviving RGCs was significantly lower in the Tg-SOD mice (596.6 ± 71.9 cells/mm2) than in the wild-type control mice (863.5 ± 68 cells/mm2). There was no difference between the numbers of surviving RGCs in the uninjured retinas of the two strains (3708 ± 231.3 cells/mm2 and 3904 ± 120 cells/mm2, respectively). Systemic injections of brimonidine significantly reduced cell death in the Tg-SOD mice, but not in the wild type. CONCLUSIONS. Overexpression of CuZnSOD accelerates RGC death after optic nerve injury in mice. Activation of the α2-adrenoreceptor pathway by brimonidine enhances survival of RGCs in an in vivo transgenic model of excessive oxidative stress.

Original languageEnglish
Pages (from-to)4169-4174
Number of pages6
JournalInvestigative Ophthalmology and Visual Science
Volume41
Issue number13
StatePublished - 2000
Externally publishedYes

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