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The Impact of MicroRNAs on Nr2e3 Associated Retinal Disease

¹Genetics Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, Nebraska
²Genetics, Cell Biology, Anatomy, Univ of Nebraska Medical Ctr, Omaha, Nebraska

Commercial Relationships: Austin S. Jelcick, None; James Reinecke, None; Yang Yuan, None; Neena B. Haider, None

Support: Grant P20-RRO18788-03, NIH Grant EY017653, NIH Hope for Vision Award

Abstract

Purpose:The purpose of this study is to evaluate the impact of microRNAs (miRNA) on Nr2e3 associated retinal disease. Nr2e3 is a critical for photoreceptor development and function. Lack of human Nr2e3 is associated with enhanced S-cone syndrome and retinitis pigmentosa, resulting in excessive production of blue opsin expressing cone cells and progressive retinal degeneration. The rd7 mouse model, lacking a functional Nr2e3 gene, exhibits a superfluous blue cone population and slow progressive retinal degeneration. Our current study examines the expression levels of potential target genes of miRNAs and their involvement in key differentially expressed gene networks.

Methods:MiRNAs were isolated at E18, P6, P14, and P30 in C57BL6/J and rd7 mice for microarray analysis. Expression levels of potential target genes of expressed miRNAs were measured by quantitative real-time PCR. Pathways analysis (Ingenuity Pathway Analysis, Ariadne Pathway Studio) of potential target genes probed relationships between these and pathways previously found to be differentially expressed between strains and temporally. Additionally, we performed immunohistochemical and western blot analysis to determine the impact of miRNA expression on protein expression and localization.

Results:We identified 15 highly significant, differentially expressed miRNAs. MicroRNA expression levels varied temporally between developmental time points, and included variations in the sensory neural miRNA cluster of 182/183/96. Potential targets also varied temporally in expression with some targets associated with retinal disease.

Conclusions:We observe temporal variations in miRNA expression and in their potential targets. These targets vary in function, including transcription, apoptosis, metabolism, and the cell cycle. This provides evidence for miRNA expression altering target gene expression, and subsequently affecting phenotypic outcome. These studies will provide additional insight into the genetic and subsequent phenotypic consequences arising as a result of miRNA expression variation.

Keywords: genetics • gene/expression • retinal development

© 2011, The Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Permission to republish any abstract or part of an abstract in any form must be obtained in writing from the ARVO Office prior to publication.