Effect of mesenchymal stem cells on the expression of interleukin-17 in the retina of experimental autoimmune uveoretinitis / 中华实验眼科杂志

ABSTRACT

BackgroundStudies determined that Th17 cells are important inflammatory cell group in experimental autoimmune uveoretinitis ( EAU ).Interleukin-17 ( IL-17 ),as a marker of Th17,is involved in the occurrence and development of EAU.Mesenchymal stem cells (MSCs) play an immunomodulatory role,mainly by inhibiting the expression of Th17 in a variety of self-autoimmune disease.This is one of the current research focuses.ObjectiveThe present study was to investigate the therapeutic effect of MSCs in EAU and their impact on IL-17 expression in the retina.MethodsMSCs were isolated from the bone marrow of the femurs from 10 SPF Wistar rats and cultured and passaged.The third to fifth generations of cells were used in this experiment.EAU models were induced in 48 6-8 week-old SPF Lewis rats by subcutaneous injection of interphotoreceptor retinoid binding protein (IRBP) R16 peptide emulsified in adjuvant.EAU rats were randomly assigned to the model control group and the MSCs group.MSCs suspension (5×106) of 1 ml was injected via the rat tail vein once a day for 3 consecutive days after immunization,and the same amount of PBS was injected in the model control group in the same manner.Six matched normal Lewis rats were used as the normal control group.The inflammatory response was clinically examined under the slit lamp biomicroscope daily,and the histopathological changes of the retina were examined by hematoxylin and eosin staining on days 9,12,15 and 20.The clinical and histopathological scoring was performed according to the Caspi criteria.Expression of the IL-17 protein in the retina was detected by immunohistochemistry on 9,12,15 and 20days following molding.The use of the animals complied with the Regulations for the Administration of Affairs Concerning Experimental Animals by Tianjin Municipality Science and Technology Commission.Results MSCs showed the fusiform in shape and vortex-like growth.Flow cytometry verified that presented the positive expression for CD29 and CD44 but absent expression for CD45 and CD34.The scores of the anterior segment were significantly lower ( U=2.815,P =0.005 ; U =2.768,P =0.006 ; U =2.900,P =0.004 ; U =2.855,P =0.004 ),and the retinal inflammation scores were lower in the MSCs group than the model control group at various time points ( U =2.345,P =0.019 ; U =2.559,P =0.011 ; U =2.166,P =0.030 ; U =2.373,P =0.018 ).Im mnunochemistry showed that the expressions levels of the IL-17 protein (A value) in the rat retina were 26.47±5.68,77.78± 9.65,47.02±6.68 and 26.59±5.94 in the MSCs group on days 9,12,15 and 20,and those in the control group were 45.34±4.63,105.95± 10.74,64.11 ±9.76 and 37.02±6.51,showing a significant reduction ( t =6.305,P =0.000 ; t =4.799,P =0.001 ; t=3.540,P=0.005;t=2.900,P=0.016). ConclusionsMSCs can inhibit the aggravation of EAU and suppress the expression of IL-17 in ocular tissue.