Large-Scale microRNA Expression Profiling Identifies Putative Retinal miRNA-mRNA Signaling Pathways Underlying Form-Deprivation Myopia in Mice.
Development of myopia is associated with large-scale changes in ocular tissue gene expression. Although differential expression of coding genes underlying development of myopia has been a subject of intense investigation, the role of non-coding genes such as microRNAs in the development of myopia is largely unknown. In this study, we explored myopia-associated miRNA expression profiles in the retina and sclera of C57Bl/6J mice with experimentally induced myopia using microarray technology. We found a total of 53 differentially expressed miRNAs in the retina and no differences in miRNA expression in the sclera of C57BL/6J mice after 10 days of visual form deprivation, which induced -6.93 ± 2.44 D (p < 0.000001, n = 12) of myopia. We also identified their putative mRNA targets among mRNAs found to be differentially expressed in myopic retina and potential signaling pathways involved in the development of form-deprivation myopia using miRNA-mRNA interaction network analysis. Analysis of myopia-associated signaling pathways revealed that myopic response to visual form deprivation in the retina is regulated by a small number of highly integrated signaling pathways. Our findings highlighted that changes in microRNA expression are involved in the regulation of refractive eye development and predicted how they may be involved in the development of myopia by regulating retinal gene expression.
Department of Ophthalmology, College of Physicians and Surgeons, Columbia University, New York, New York, United States of America.|Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, New York, United States of America.
Andrei V
AV
Tkatchenko
Department of Ophthalmology, School of Medicine, Duke University, Durham, North Carolina, United States of America.|Center for Human Genetics, School of Medicine, Duke University, Durham, North Carolina, United States of America.
Xiaoyan
X
Luo
Department of Ophthalmology, College of Physicians and Surgeons, Columbia University, New York, New York, United States of America.
Tatiana V
TV
Tkatchenko
Bioinformatics Institute, Agency for Science Technology and Research, Singapore, Singapore.
Candida
C
Vaz
Bioinformatics Institute, Agency for Science Technology and Research, Singapore, Singapore.|Institute for Medical Biology, A*STAR, Singapore, Singapore.
Vivek M
VM
Tanavde
Bioinformatics Institute, Agency for Science Technology and Research, Singapore, Singapore.
Sebastian
S
Maurer-Stroh
Department of Mechanical Engineering and Materials Science, Pratt School of Engineering, Duke University, Durham, North Carolina, United States of America.
Stefan
S
Zauscher
Department of Ophthalmology, School of Medicine, Duke University, Durham, North Carolina, United States of America.
Pedro
P
Gonzalez
Department of Ophthalmology and Visual Sciences, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin, United States of America.
Terri L
TL
Young
D000818:Animals; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009216:Myopia / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D010775:Photic Stimulation; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D012160:Retina / Q000378:metabolism; D012590:Sclera / Q000378:metabolism; D012683:Sensory Deprivation; D015398:Signal Transduction / Q000235:genetics
D035683:MicroRNAs; D012333:RNA, Messenger