Dynamic changes of microRNAs in the eye during the development of experimental autoimmune uveoretinitis.
OBJECTIVE
Interleukin (IL)-17-producing Th17 cells play a crucial role in the development of experimental autoimmune uveoretinitis (EAU). Recent studies revealed that the production of cytokines such as IL-17 is controlled by microRNA (miRNA). Here the authors investigated the expression of miRNA in the eye during the development of EAU.


METHODS
To induce EAU, B10.RIII mice were injected with interphotoreceptor retinoid binding protein peptide 161-180 with adjuvants. Control mice received adjuvants alone. Seven, 14, 21, or 28 days after immunization, eyes were harvested for histologic analysis, miRNA array, quantitative real-time polymerase chain reaction (qRT-PCR) for cytokines and miRNAs, and in situ hybridization for miRNAs. Expression levels of cytokines and miRNAs were compared with control mice.


RESULTS
No histologic changes were observed in eyes collected at day 7. At day 14, EAU was most severe, and thereafter retinal structure was gradually destroyed. Retinal inflammation was not observed in control mice. IL-17A and IL-17F were significantly higher in the eyes of EAU-induced mice at day 7. Array analysis followed by qRT-PCR revealed that in EAU-induced mice, miRNA-142-5p and miRNA-21 were significantly higher, whereas miRNA-182 was significantly lower. These changes could be detected 7 days after EAU induction. In situ hybridization analysis for these miRNAs confirmed qRT-PCR data.


CONCLUSIONS
Expression changes in three miRNAs could be detected in the eye before histologic EAU. Kinetic changes of these miRNAs in the eye paralleled those of IL-17. The possibility that miRNAs can affect IL-17 suggests that miRNAs in the retina regulate the development of EAU.
Ishida
Waka
W
Department of Ophthalmology, Science Research Center, Kochi Medical School, Nankoku, Japan.
Fukuda
Ken
K
Higuchi
Takuma
T
Kajisako
Mina
M
Sakamoto
Shuji
S
Fukushima
Atsuki
A
D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics*; D016207:Cytokines / Q000235:genetics; D004195:Disease Models, Animal; D005136:Eye Proteins; D020869:Gene Expression Profiling; D017403:In Situ Hybridization; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D046228:Microarray Analysis; D012333:RNA, Messenger / Q000235:genetics; D012173:Retinitis / Q000235:genetics*; D012177:Retinol-Binding Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014605:Uveitis / Q000235:genetics*; D000099214:Retinol-Binding Proteins, Interstitial
D016207:Cytokines; D005136:Eye Proteins; D035683:MicroRNAs; D012333:RNA, Messenger; D012177:Retinol-Binding Proteins; D000099214:Retinol-Binding Proteins, Interstitial