Genistein, a protein tyrosine kinase inhibitor, ameliorates retinal degeneration after ischemia-reperfusion injury in rat.

This content is PDF only. Please click on the PDF icon to access.

Abstract

PURPOSE: The authors sought to determine the effect of genistein, a naturally occurring protein tyrosine kinase inhibitor, in a model of ischemia-reperfusion injury in the rat retina. METHODS: Ischemia-reperfusion injury was induced by temporary optic nerve ligation. A dose of 0.034 mg, 0.34 mg, and 3.4 mg of genistein or dimethyl sulfoxide (DMSO) alone was injected intraperitoneally 1 hour before the ligation of the optic nerve and just after the start of reperfusion. After 48 hours of reperfusion, the effect of genistein on overall protein tyrosine phosphorylation in the retina was studied using Western blot analysis. After 168 hours, the effect of increasing doses of genistein on retinal degeneration was examined by quantitative morphometric analysis of histologic sections of the retina. RESULTS: The authors found that tyrosine phosphorylation was increased after 48 hours of reperfusion in the ischemia-reperfusion-injured eyes treated with DMSO alone. A severe inner retinal degeneration was observed in the animals treated with DMSO alone after 168 hours of reperfusion. The treatment with 3.4 mg genistein inhibited the increase in tyrosine phosphorylation and protected the eyes significantly from the induced ischemic retinal degeneration by morphometric analysis of the mean thickness of the inner limiting membrane to the outer limiting membrane, the inner plexiform layer, and the inner nuclear layer (P < 0.02). Treatments with lower amounts of genistein (0.034 mg and 0.34 mg) did not show a significant protection of retinal degeneration after the injury. CONCLUSIONS: Systemic administration of high dose of genistein, a dietary-derived isoflavone, can ameliorate an ischemia-reperfusion-induced retinal degeneration. Genistein may be useful to prevent neuronal degeneration in the inner retina as a result of ischemic injury.