Interleukin-6 protects retinal ganglion cells from pressure-induced death
Interleukin-6 protects retinal ganglion cells from pressure-induced death
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DOI：
10.1167/iovs.05-1407
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发表时间：
2006-07-01
影响因子：
4.4
通讯作者：
Calkins, David J.
中科院分区：
文献类型：
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作者：
Sappington, Rebecca M.;Chan, Matilda;Calkins, David J.
目的。青光眼视网膜神经节细胞（RGCs）对眼压的反应可能涉及星形胶质细胞和小胶质细胞的信号。研究神经胶质源性因子如何影响RGC在常温和高压下的存活，以及炎症细胞因子白细胞介素-6 （IL-6）是否与之相关。采用免疫磁分离法制备视网膜星形胶质细胞、小胶质细胞和RGCs原代培养物。比较了RGC在常温和高压（+70 mm Hg）下的存活情况，以及在含有il -6和il -6缺失的胶质细胞压力条件培养基下的存活情况。压力升高24 - 48小时可降低RGC密度，增加TUNEL标记，上调几个凋亡基因，包括早期直接基因c-jun和jun-B。星形胶质细胞的压力条件培养基使RGC的存活率又降低了38%，而小胶质细胞培养基使RGC的存活率恢复到环境水平。这些影响与小胶质细胞培养基中的IL-6无关。星形胶质细胞和小胶质细胞条件的培养基都不会影响周围RGC的存活，除非IL-6被耗尽，后者分别导致RGC减少63%和18%。与胶质细胞条件培养基中IL-6水平相当的重组IL-6在高压下使RGC存活增加了一倍。对于处于环境压力下的rgc，星形胶质细胞和小胶质细胞分泌的IL-6足以减弱这些胶质细胞的其他促凋亡信号。对于受到高压刺激的RGCs，星形胶质细胞培养基中IL-6的减少不足以抵消这些信号。小胶质细胞中IL-6的增加不仅抑制了这些细胞的促凋亡信号，而且抑制了rgc固有的压力诱导的凋亡级联。
PURPOSE. The response of retinal ganglion cells (RGCs) to ocular pressure in glaucoma likely involves signals from astrocytes and microglia. How glia-derived factors influence RGC survival at ambient and elevated pressure and whether the inflammatory cytokine interleukin-6 (IL-6) is a contributing factor were investigated.METHODS. Primary cultures of retinal astrocytes, microglia, and RGCs were prepared using immunomagnetic separation. Comparisons were made of RGC survival at ambient and elevated pressure (+70 mm Hg) and with pressure-conditioned medium from glia with, and depleted of, IL-6.RESULTS. Pressure elevated for 24 to 48 hours reduced RGC density, increased TUNEL labeling, and upregulated several apoptotic genes, including the early immediate genes c-jun and jun-B. Pressure-conditioned medium from astrocytes reduced RGC survival another 38%, while microglia medium returned RGC survival to ambient levels. These effects were unrelated to IL-6 in microglia medium. Neither astrocyte-nor microglia-conditioned medium affected ambient RGC survival unless depleted of IL-6, which induced a 63% and a 18% decrease in RGCs, respectively. Recombinant IL-6 equivalent to levels in glia-conditioned medium doubled RGC survival at elevated pressure.CONCLUSIONS. For RGCs at ambient pressure, IL-6 secreted from astrocytes and microglia under pressure is adequate to abate other proapoptotic signals from these glia. For RGCs challenged by elevated pressure, decreased IL-6 in astrocyte medium is insufficient to counteract these signals. Increased IL-6 in microglia medium counters not only proapoptotic signals from these cells but also the pressure-induced apoptotic cascade intrinsic to RGCs.