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A. Hirata, Y. Inomata, N. Yonemura, T. Koga, N. Kido, H. Tanihara; Interleukin-6 Combined with Soluble Interleukin-6 Receptor Inhibits Neuronal Cell Death by NMDA in Rat Retinas . Invest. Ophthalmol. Vis. Sci. 2003;44(13):5207.
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Purpose: To determine if interleukin-6 (IL-6) combined with soluble Interleukin-6 receptor (sIL-6R) modulates N-methyl-D-aspartate (NMDA)-induced retinal damage. Methods:Eyes of Sprague-Dawley rats pretreated with a combined injection IL-6 (5 to 500 ng/eye) and sIL-6R (2.5 to 250 ng/eye) was administered with NMDA (20 nmol) into the vitreous cavity. PBS were injected as control. Each eye was enucleated and transverse sections were subjected to morphometric analysis. The degree of NMDA-induced retinal neuronal death was quantified by cell counts in the ganglion cell layer (GCL) and by the thickness of the inner plexiform layer (IPL). Retrograde labeling with a fluorescent tracer (fluoro-Gold) was applied for counting survival retinal ganglion cells (RGCs). Apoptotic changes in the retina were assessed by the TUNEL method. Western blotting analysis was perfomed for examination of gp130 in NMDA injected retina. Results:Treatment with IL-6 only, or sIL-6R did not bring neuroprotective effects against NMDA-induced retinal damage. However, pretreatment with IL-6 (5-500ng) combined with sIL-6R (2.5-250ng) induced significant neuroprotective effects on NMDA-induced retinal damage. The differences between the numbers for the GCLs and the thickness of the IPL in PBS- and combined IL-6 with sIL-6R-injected eyes were statistically significant.(p<0.05, p<0.005). In analysis of retrograde labeling of RGCs, at 7 days after NMDA was injected into the eyes, the mean densities for the RGCs of control (PBS-injected) and experimental (50 ng IL-6 and 25 ng sIL-6R, 5 ng IL-6 and 2.5 ng sIL-6R-pretreated) were statistically significant.(p<0.005, p<0.005). In TUNEL method, pretreatment with IL-6 combined with sIL-6R prevents NMDA induced apoptosis. Western blotting studies demonstrated upregulation of gp130 expression in NMDA-injected retina. Conclusions:Present studies suggest that IL-6 combined with sIL-6R provides neuroprotective effects on NMDA-induced retinal damage.
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