Therapeutic effects of rapamycin on experimental autoimmune uveoretinitis / 中华实验眼科杂志

ABSTRACT

Background Studies determined that rapamycin has not only the antibiosis but also suppressing the auto-immunology.The treating effect of rapamycin on experimental autoimmune uveoretinitis (EAU) is still concerned.Objective This work was to investigate the therapeutic effect of rapamycin on EAU and study the effect on the expression of inflammatory cytokines which were secreted by T lymphocyte subgroup in EAU.Methods EAU was induced in 20 SPF male Lewis rats by subcutaneous injection of interphotoreceptor retinoid binding protein (IRBP) R16 peptide emulsified in adjuvant.The rats were randomized into model control group and rapamycin injection group and 10 rats for each group.The rapamycin of 0.2 mg/( kg · d) 0.4 ml was intraperitoneally injected for the consecutive 7 days immediately after modeling,and the equal volume of normal saline solution was used at the same fashion in the model control group and 5 normal matched rats( normal control group).The ocular manifestation of the rats were examined under the slit lamp regularly.The retinal sections of the rats were prepared in the 14 days after modeling for the histopathological examination with hematoxylin and eosin staining.The ocular signs of inflammation and histopathological severity were scored based on the criteria of Caspi.Expression of interferon-γ (IFN-γ) and interleukin-17 (IL-17) in rat retinas were detected by immunohistochemistry.This experiment followed the Regulation for the Administration of Affair Concerning Experimental Animals by Tianjin Municipal Government.Results The scores of ocular signs elevated gradually from 6 through 12 days after modeling and slowly declined after that in the model control group.A same tendency was seen in the rapamycin injection group.The significant differences were seen in the scores of ocular signs between the two groups from 6 to 14 days( P＜0.01 ).The disorder of retinal structure and infiltration of inflammatory cells were seen in the model control group,but the retina layers were normal in the rapamycin injection group.The pathological score was evidently declined in the rapamycin injection group ( 0.90 ± 0.45 ) in comparison with model control group( 3.30±0.48 ) ( t =16.541,P＜0.01 ).The expressions of the IFN-γ and IL-17 in retina located in the outer nuclear layer,inner nuclear layer,internal plexiform layer and retinal ganglion cell layer with the weakened levels(A values) in rapamycin injection group compared with model control group,showing a considerably difference between them ( IFN-γ21.16±4.23 vs 62.14 ±7.32; IL-1749.86±6.59 vs 124.85 ±6.33 )(q=33.334,q=56.923,P＜0.01 ).Conclusions Rapamycin down-regulates the expressions of IFN-γ and IL-17 in retina and further eliminates the inflammatory response in the rat with EAU by the suppression of Th1 and Th17 cells function in EAU.