Altered retinal microRNA expression profile in a mouse model of retinitis pigmentosa
| Autor: | Alasdair Ivens, Karsten Hokamp, G. Jane Farrar, Arpad Palfi, Carol J. Loscher, Peter Humphries, Paul F. Kenna |
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| Rok vydání: | 2007 |
| Předmět: |
Retinal degeneration
genetic structures Biology Photoreceptor cell Retina 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Retinitis pigmentosa microRNA medicine Animals GeneralLiterature_REFERENCE(e.g. dictionaries encyclopedias glossaries) 030304 developmental biology 0303 health sciences Reverse Transcriptase Polymerase Chain Reaction Gene Expression Profiling Research Retinal MicroRNA Expression Profile medicine.disease Molecular biology eye diseases 3. Good health Cell biology Gene expression profiling Ophthalmology Disease Models Animal MicroRNAs medicine.anatomical_structure chemistry sense organs 030217 neurology & neurosurgery Retinitis Pigmentosa |
| Zdroj: | Genome Biology |
| ISSN: | 1474-760X |
| Popis: | PUBLISHED Background The role played by microRNAs (miRs) as common regulators in physiologic processes such as development and various disease states was recently highlighted. Retinitis pigmentosa (RP) linked to RHO (which encodes rhodopsin) is the most frequent form of inherited retinal degeneration that leads to blindness, for which there are no current therapies. Little is known about the cellular mechanisms that connect mutations within RHO to eventual photoreceptor cell death by apoptosis. Results Global miR expression profiling using miR microarray technology and quantitative real-time RT-PCR (qPCR) was performed in mouse retinas. RNA samples from retina of a mouse model of RP carrying a mutant Pro347Ser RHO transgene and from wild-type retina, brain and a whole-body representation (prepared by pooling total RNA from eight different mouse organs) exhibited notably different miR profiles. Expression of retina-specific and recently described retinal miRs was semi-quantitatively demonstrated in wild-type mouse retina. Alterations greater than twofold were found in the expression of nine miRs in Pro347Ser as compared with wild-type retina (P < 0.05). Expression of miR-1 and miR-133 decreased by more than 2.5-fold (P < 0.001), whereas expression of miR-96 and miR-183 increased by more than 3-fold (P < 0.001) in Pro347Ser retinas, as validated by qPCR. Potential retinal targets for these miRs were predicted in silico. Conclusion This is the first miR microarray study to focus on evaluating altered miR expression in retinal disease. Additionally, novel retinal preference for miR-376a and miR-691 was identified. The results obtained contribute toward elucidating the function of miRs in normal and diseased retina. Modulation of expression of retinal miRs may represent a future therapeutic strategy for retinopathies such as RP. This research was supported by funds from Health Research Board of Ireland (RP/2006/131 and H01188) and Rare Diseases Fellowship, Health Research Board of Ireland and Fighting Blindness of Ireland (RF-RD-05-05). |
| Databáze: | OpenAIRE |
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