Purchase this article with an account.
Caroline E. Haldin, Philip J. Horner, Shunbin Xu; Retinal miRNAs in Normal Aging and Glaucomatous Neurodegeneration. Invest. Ophthalmol. Vis. Sci. 2012;53(14):3872.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
microRNAs (miRNAs) are small, non-coding RNAs, that regulate gene expression through their target sites in the 3’ untranslated regions (UTRs) of downstream mRNAs, causing mRNA degradation and/or reduction in translation. Glaucoma is a progressive neurodegenerative eye disease due to dysfunction and death of retinal ganglion cells (RGCs) and degeneration of optic nerve. To date, miRNAs’ involvement in glaucoma has not been fully studied. This study aims to examine the roles of miRNAs in the retina during the development of glaucoma using a mouse model, the DBA/2J (D2) mouse, a surrogate animal model for human glaucoma.
Total RNA was isolated from retinas of D2 mice at four- (pre-disease, with IOPs near or below the colony average), eight- (after detectable signs of glaucoma with elevated IOPs) and eleven months of age (after IOPs are elevated, signs of glaucoma have fully developed) and their sibling control, D2-Gpnmb+ mice, using mirVana™ miRNA isolation kit (Ambion). Rodent Taqman low-density arrays v3.0 were used to profile 754 miRNAs on a 7900HT Fast Real-Time PCR System. Expression profiles were acquired using RQ Manager software with automatic baseline and RQ threshold set at 0.2. Statistical analysis was carried out using DataAssist v2 (Applied Biosystems).
429-445 miRNAs were detected in the retina of D2 and control mice at all ages. At four months old, only six miRNAs were differentially expressed (p<0.05), two of which had more than 2-fold change, suggesting little miRNA-expression changes at the pre-disease stage. At eight- and 11-months, increasing numbers of miRNAs were differentially expressed in the retina, with 13 and 17 differentially expressed at 8 and 11 months old (p<0.05), respectively. In addition, we identified a series of miRNAs whose expression levels changed at different ages of control and D2 mice. Currently, miRNA expression levels, localization, target sequence and function are being confirmed.
miRNA expression in the retina changes during normal aging and development of glaucoma. Further characterization of these differentially expressed miRNAs may identify miRNAs involved in the pathogenesis of glaucomatous neurodegeneration. Our ongoing study on miRNAs in optic nerve head (ONH) and retinal ganglion cells (RGCs) isolated by laser-capture microdissection (LCM) will further elucidate the roles in the development of glaucoma.
This PDF is available to Subscribers Only