Tohoku J. Exp. Med., 1999, 187 (3)

Administration of Nerve Growth Factor, Brain-Derived Neurotrophic Factor and Insulin-Like Growth Factor-II Protects Phosphate-Activated Glutaminase in the Ischemic and Reperfused Rat Retinas

HIROSHI TOMITA, SEI-ICHI ISHIGURO, TOSHIAKI ABE and MAKOTO TAMAI

Department of Ophthalmology, Tohoku University School of Medicine, Sendai 980-8574

  • Phosphate-activated glutaminase (PAG) activity decreases markedly in the early period of ischemia. The decrease of the enzyme activity is reversible if the ischemic period is relatively short, but it becomes irreversible after 90 minutes of ischemia. The deterioration is a functional damage of the retinas caused by ischemia. We studied effects of growth factors and neurotrophic factors on protection of PAG in the ischemic and reperfused rat retinas. Before ischemia, 1 ml of growth factors or neurotrophic factors (0.1 mg/ml for insulin-like growth factor-I [IGF-I], insulin-like growth factor-II [IGF-II], brain-derived neurotrophic factor [BDNF], nerve growth factor [NGF]; 1 mg/ml for basic fibroblast growth factor [bFGF]) were injected into the vitreous cavity of the left eyes of anesthetized Sprague Dawley rats. As a control, phosphate buffered saline was injected to the right eyes. To induce ischemia, we clamped left eyes for 90 minutes after bulbar conjunctival incision all around limbus. The rat retinas were homogenized with distilled water 1 day after reperfusion and used for PAG assay. Retinal ammonia concentration was also determined as a ischemic marker. About 80% decrease of retinal PAG activity and 50% increase of retinal ammonia concentration were observed after 90 minutes of ischemia and 1 day of reperfusion as compared with unoperated normal eyes. IGF-II, BDNF and NGF had protective effects on the retinal PAG activity, whereas IGF-I, bFGF, stable bFGF were less effective. In addition, IGF-II and BDNF suppressed elevation of retinal ammonia concentration. BDNF, NGF and IGF-II have marked effect on the protection of PAG activity in the ischemic and reperfused rat retinas, whereas bFGF, which is very effective for the protection of ischemic cell death, shows moderate effect.
    Key words--- ischemia; phosphate-activated glutaminase; ammonia; growth factors
    © 1999 Tohoku University Medical Press

    Tohoku J. Exp. Med., 1999, 187, 227-236
    Address for reprints: Hiroshi Tomita, Ph.D., Department of Ophthalmology, Tohoku University School of Medicine, 1-1 Seiryomachi Aoba-ku, Sendai 980-8574, Japan.
    e-mail: h-tomita@oph.med.tohoku.ac.jp
    Present address for Sei-ichi Ishiguro, Department of Biochemistry and Biotechnology, Faculty of Agriculture and Life Science, Hirosaki University, 3 Bunkyo-cho, Hirosaki 036-8224, Japan.
    For reprints request, contact S. Ishiguro at the address above.

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