IL-17A mediates inflammation-related retinal pigment epithelial cells injury via ERK signaling pathway

AIM:To investigate whether interleukin-17A(IL-17A)gets involved in the mechanisms of inflammation-related retinal pigment epithelium(RPE)cells injury and its significance in age-related macular degeneration(AMD).MRTHODS:A sodium iodate(NaIO3)mouse model as well as IL-17A-/-mice were established.The effects of inflammatory cytokines in RPE cells and retinal microglia before and after NaIO3 modeling in vivo and in vitro,were investigated using immunofluorescence,immunoprotein blotting,and quantitative real-time fluorescence polymerase chain reaction(qRT-PCR),respectively.Interventions using recombinant IL-17A protein(rIL-17A)or IL-17A neutralizing antibody(IL-17A NAb)were used to observe the subsequent differences in fundus,fundus photography and optical coherence tomography(OCT),cell viability,and expression of oxidative stress-related markers before and after modeling,and to screen for key signaling pathways.RESULTS:In the scenario of NaIO3 stimulation,RPE cells obviously tended to degenerate.Simultaneously proliferation and activation of retinal microglia was confirmed in NaIO3-stimulated mice,whereas such effects induced by NaIO3 were significantly ameliorated with IL-17A NAb intervention or in IL-17A-/-mice.In addition,IL-17A promoted the proliferation and activation of microglia as well as oxidative damage and the secretion of inflammatory cytokines alongside NaIO3-induced damage in RPE cells in vivo and ex vivo.Meanwhile,the extracellular signalregulated kinase(ERK)signaling pathway was shown to be participated in the regulation of NaIO3-induced RPE cells injury mediated by IL-17A in vivo and ex vivo,as IL-17A induced inflammatory cytokines release in the NaIO3 model was alleviated after blocking the ERK pathway.CONCLUSION:IL-17A probably promotes the NaIO3-induced RPE cells injury through exacerbating inflammation in terms of retinal microglia activation and inflammatory cytokines release via ERK signaling pathway.Inhibition of IL-17A may be a new potential target for dry AMD treatment.

骨髓间充质干细胞在视网膜色素变性大鼠视网膜下的分化(英文)

目的:研究骨髓间充质干细胞(MSC)在视网膜色素变性(RP)大鼠体内的分化。方法:Lewis大鼠腹腔注射30g/L NaIO_3 100mg/kg,建立大鼠RP模型,将体外培养的MSC植入视网膜下腔,用免疫荧光标记的方法对MSC进行追踪,并观察术后第1,2,3,4,5wk MSC在该微环境中的分化。结果:术后第1wk即可见MSC位于视网膜色素上皮(RPE)层与光感受器细胞层,但全角蛋白(PCK)及rhodopsin标记阴性,第3wk开始可见MSC在体内表达PCK及rhodopsin。结论:MSC植入RP模型大鼠视网膜下腔后可存活,主要分布于RPE层和视锥、视杆细胞层,并表达RPE细胞和光感受器细胞的表面标志。

骨髓间充质干细胞在碘酸钠注射大鼠视网膜下的分化

目的研究骨髓间充质干细胞(BMMSCs)在视网膜色素上皮(RPE)受损的大鼠模型眼中的分化情况。方法体外培养Wistar大鼠的BMMSCs,用病毒上清液转染EGFP,移植到经静脉注射NaIO3破坏RPE细胞的大鼠的视网膜下腔,用免疫荧光标记的方法对BMMSCs进行追踪并观察术后5周的分化情况。结果BMMSCs的EGFP转染比例可达到76·9%,术后第5周可见BMMSCs位于视网膜下区域,未整合入神经视网膜层,并表达角蛋白(CK)、视紫红质(rhodopsin)和胶质纤维酸性蛋白(GFAP)。结论BMMSCs植入RPE受损伤的大鼠视网膜下腔后可存活,并表达RPE细胞、光感受器细胞和星形胶质细胞的特异性标志。

骨髓间充质干细胞在视网膜色素变性大鼠视网膜下的分化

目的研究骨髓间充质干细胞(MSCs)在视网膜色素变性(RP)大鼠体内的分化。方法Lewis大鼠腹腔注射3%NaIO3100mg/kg,建立大鼠RP模型,将体外培养的MSCs植入视网膜下腔,用免疫荧光标记法对MSCs进行追踪,并观察术后第1、2、3、4、5周MSCs在该微环境中的分化。结果术后第1周即可见MSCs位于视网膜色素上皮(RPE)层与光感受器细胞层,但全角蛋白(PCK)及Rhodopsin标记阴性,第3周开始可见MSCs在体内表达PCK及Rhodopsin。结论MSCs植入RP模型大鼠视网膜下腔后可存活,主要分布于RPE层和视锥、视杆细胞层,并表达RPE细胞和光感受器细胞的表面标志。