Protective effect of adult T-cell leukemia-derived factor on retinal ischemia-reperfusion injury in the rat.

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Abstract

PURPOSE: To evaluate the protective effects of recombinant adult T-cell leukemia- derived factor (ADF)-human thioredoxin against ischemia-reperfusion injury in the rat retina. METHODS: Retinal ischemia was induced in rats by increasing the intraocular pressure to 110 mm Hg for 60 minutes. Various doses of recombinant human ADF (rhADF) or vehicle were administered intravenously before ischemia induction and immediately after reperfusion. The degree of retinal damage was assessed by electroretinogram (ERG) recording, by measuring the inner retinal thickness, and by counting the number of TdT-dUTP terminal nick-end labeling (TUNEL)-positive cells in the inner nuclear layer. RESULTS: The amplitudes of the ERG b-wave and oscillatory potentials were increased significantly by treatment before ischemia and after reperfusion with 0.5 mg or 5 mg rhADF and by treatment after reperfusion with 1 mg rhADF, compared with those of vehicle-treated control rats (P < 0.01). On day 28 after reperfusion, the thickness of the inner retina of control rats and of rats treated before ischemia and after reperfusion with 0.5 mg rhADF were 46.1+/-6.4 microm and 78.5+/-8.9 microm, respectively (P < 0.01). The number of TUNEL-positive cells on days 1 and 2 after reperfusion was decreased significantly by treatments with 0.5 mg rhADF compared with the number of TUNEL-positive cells in control rats (P < 0.01). CONCLUSIONS: Electrophysiologic and histologic studies showed that ischemia for 60 minutes produces severe damage in vehicle-treated control rat retina, particularly in the inner retinal layer. Intravenous injection of rhADF protects the rat retina from ischemia-reperfusion injury.