Abstract
Purpose:
We previously showed that mesenchymal stem cells (MSCs) can ameliorate EAU and reduced tissue impairment. This study tested the hypothesis that the exosomes derived from MSCs could reduce the severity of EAU as their parent cells.
Methods:
EAU was induced by immunization with interphotoreceptor retinoid-binding protein 1177-1191 (R16) in Lewis rat. Exosomes were purified from supernatants of human umbilical cord MSCs by multistep gradient centrifugations and ultrafiltrations. The animals immunized with R16 were then treated with MSC-derived exosomes by periocular injection starting from the onset of ocular inflammation (day 9) to day 14 post-immunization. Clinical signs were daily examined by slit-lamp, and ocular histology and electrophysiology (ERG) were evaluated at different time points. The infiltration of T cell subsets and macrophage were determined using flow cytometry and immunochemistry respectively. Splenocytes were collected from both naïve and EAU rats, and the chemotactic suppression of exosomes on NKs, NKTs, neutrophils, and macrophages was examined by a transwell system.
Results:
Exosome therapy significantly reduced the inflammatory intensity of ongoing EAU. Both clinical and histological scores were significantly lower in treatment group than those in control group (P＜0.05) with reduced infiltrating Th1, Th17 cells and macrophages in the former. In addition, ERG in the treated group was remarkable ameliorated compared to the control group. Chemotaxis assay showed that MSC derived exosomes suppressed the chemoattractive effects of CCL2 and CCL-21 on NK, NKT, Gr-1+, and CD68+cells (P＜0.05).
Conclusions:
Like their parent cells, exosomes derived from MSCs can reduce intraocular inflammation when administered during the onset of EAU. Because of the unique features of exosomes, they might replace their cells for therapeutic intervention in uveitis. Further experiments are undergoing to explore the possible inhibitory mechanisms of MSC derived exosomes on EAU.