MicroRNA Expression in the Glaucomatous Retina

Jayaram, Hari; Cepurna, William O.; Johnson, Elaine C.; Morrison, John C.

doi:10.1167/iovs.15-18088

Cited by 60Glaucoma and retinal disordersMicroRNA in disease regulationRetinal Imaging and Analysis

MicroRNA Expression in the Glaucomatous Retina

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Jayaram, Hari, Cepurna, William O., Johnson, Elaine C., Morrison, John C.·2015·Investigative Opthalmology & Visual Science

DOI 10.1167/iovs.15-18088PMC PMC4684194

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Abstract

PURPOSE: MicroRNAs are small, endogenous noncoding RNAs that modulate posttranscriptional gene expression. Although the contribution of microRNAs to the pathogenesis of glaucomatous damage is unknown, supporting evidence from central nervous system (CNS) research suggests they may play a role. It was therefore hypothesized that microRNAs known to be altered in CNS injury are also altered in experimental glaucoma. METHODS: Intraocular pressure (IOP) was elevated in rats by unilateral injection of hypertonic saline and IOP monitored for 5 weeks. After rats were killed, retrobulbar optic nerve sections were graded for damage. MicroRNA was extracted from whole retinae of eyes with advanced nerve damage (n = 8) and from normal, noninjected control eyes (n = 8). Quantitative PCRs were performed using a panel of 17 microRNAs, reported from CNS research to be implicated in mechanisms also linked to glaucomatous damage. Computationally and experimentally derived gene targets were identified for the differentially expressed microRNAs. These were then integrated with existing gene array data. Functional interpretation was performed using the Molecular Signatures Database and DAVID Functional Annotation Clustering. RESULTS: Eight microRNAs were significantly downregulated in glaucomatous retinae compared with controls (miR-181c, miR-497, miR-204, let-7a, miR-29b, miR-16, miR106b, and miR-25); miR-27a was significantly upregulated. Enrichment of targets associated with extracellular matrix/cell proliferation, immune system, and regulation of apoptosis were observed. Cholesterol homeostasis and mTORC-1 pathways showed reduced expression. CONCLUSIONS: MicroRNAs are differentially expressed in retinae of eyes with advanced glaucomatous damage compared with normal controls. Integrating microRNA with gene expression data may improve understanding of the complex biological responses produced by chronically elevated IOP.

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Authors: Jayaram, H., Cepurna, W. O., Johnson, E. C., & Morrison, J. C.
Affiliations: Oregon Health & Science University (US)
Corresponding author: Morrison, John C.
ORCID: Jayaram, Hari
Cepurna, William O.
Venue: Investigative Opthalmology & Visual Science
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Published: 2015-12-17
Volume: 56
Issue: 13
Pages: 7971
ISSN: 0146-0404 (ISSN-L)
1552-5783
DOI: 10.1167/iovs.15-18088
PMC: PMC4684194
OpenAlex: W992567281
Semantic Scholar: 9d81f90260dd24afd4b41a665ae6abd2c8141821
Cited by: 60
References: 98
Citations by year: 2026: 1 · 2025: 5 · 2024: 9 · 2023: 8 · 2022: 3 · 2021: 12 · 2020: 7 · 2019: 2 · 2018: 4 · 2017: 7 · 2016: 2
FWCI: 3.93
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Investigative Ophthalmology & Visual Science (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
UCL Discovery (University College London) (submittedVersion)
Funders: Research to Prevent Blindness (P30 EY010572)
Oregon Health and Science University (P30EY010572)
US-UK Fulbright Commission
Moorfields Eye Hospital NHS Foundation Trust
National Institutes of Health
Allergan
National Eye Institute (R01EY010145, P30EY010572)
Topics: Health Sciences › Medicine › Ophthalmology › Glaucoma and retinal disorders
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Retinal Imaging and Analysis
Keywords: microRNA expression, glaucoma, retina, intraocular pressure elevation, optic nerve injury, miR-181c, miR-497, miR-204, let-7a, miR-29b, miR-16, miR-106b, miR-25, miR-27a, miRNA target genes, extracellular matrix, apoptosis, cholesterol homeostasis, mTORC1 signaling, gene expression data integration
MeSH terms: Animals, Disease Models, Animal, Glaucoma, Male, Retina, Retinal Ganglion Cells, Polymerase Chain Reaction, MicroRNAs, Rats

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