Purchase this article with an account.
Ravi Metlapally, Pedro Gonzalez, Felicia Hawthorne, Khanh-Nhat Tran-Viet, Christine F. Wildsoet, Terri L. Young; Micro-RNAs in the Sclera: Role in Ocular Growth, and Implications for Myopia. Invest. Ophthalmol. Vis. Sci. 2012;53(14):5141.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
The socio-economic impact of myopia on our society is significant. Ocular axial elongation during myopia development is driven by a retino-scleral signaling cascade and guided by scleral extracellular matrix remodeling. Micro-RNAs (miRNAs) regulate gene expression by pairing with the 3’UTR of target sequences, and serve as nodes of signaling networks. We hypothesized that the sclera, like most tissues, expresses miRNAs, and that some may play an active role in ocular growth regulation.
Scleral samples from normal human fetal (24 week gestation) and adult (age-matched) donor eyes (n=3, each group) were obtained. RNA was extracted using the miRVANA kit and genome-wide miRNA profiling performed using the Agilent Human miRNA Microarray platform. Microcosm, TargetScan and PicTar algorithms were used to obtain miRNA target predictions. Follow-up experiments using TaqMan® MicroRNA Assays targeting select micro-RNAs were applied to tissue from posterior and peripheral scleral regions (n=7, each group). Microarray data were analyzed using miRInform, and quantitative PCR data with 2^-deltaCt method.
Human sclera expressed approximately 300 miRNAs (298 & 353 detected in at least one adult and fetal sclera sample respectively), with several miRNAs showing differential regulation (p<0.01, min p=1.5x106). Of the miRNAs examined further, mir-214, let-7c, let-7e, mir-103, mir-107, and mir-98 showed increased expression in fetal tissue (fold changes 1.5 to 4, p<0.01). No significant differences were observed in miRNA expression between posterior and peripheral regions within either age group.
To our knowledge, this is the first study of micro-RNA expression in human sclera. Of the miRNAs identified, many showed age- and presumed growth-related differential regulation, higher in rapidly growing fetal eyes, consistent with a role in ocular growth regulation. A link between these scleral micro-RNAs and myopia, which also involves rapidly elongating eyes, is plausible but yet to be established. Genome-wide mRNA profiling is underway to characterize the pathways involved and the correlation with micro-RNA signatures.
This PDF is available to Subscribers Only