Escher, Pascal; Schorderet, Daniel F; Cottet, Sandra (2011). Altered expression of the transcription factor Mef2c during retinal degeneration in Rpe65-/- mice. Investigative ophthalmology & visual science, 52(8), pp. 5933-5940. Association for Research in Vision and Ophthalmology 10.1167/iovs.10-6978
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PURPOSE
To investigate the role of the myocyte enhancer factor 2 (Mef2) transcription factor family in retinal diseases, Mef2c expression was assessed during retinal degeneration in the Rpe65(-/-) mouse model of Leber's congenital amaurosis (LCA). Mef2c-dependent expression of photoreceptor-specific genes was further addressed.
METHODS
Expression of Mef2 members was analyzed by oligonucleotide microarray, quantitative PCR (qPCR), and in situ hybridization. Mef2c-dependent transcriptional activity was assayed by luciferase assay in HEK293T cells.
RESULTS
Mef2c was the only Mef2 member markedly downregulated during retinal degeneration in Rpe65(-/-) mice. Mef2c mRNA level was decreased by more than 2-fold at 2 and 4 months and by 3.5-fold at 6 months in retinas of Rpe65(-/-) mice. Downregulation of Mef2c at the protein level was confirmed in Rpe65(-/-) retinas. The decrease in Mef2c mRNA levels in the developing Rpe65(-/-) retinas from postnatal day (P) 13 onward was concomitant with the decreased expression of the rod-specific transcription factors Nrl and Nr2e3. Nrl was further shown to drive Mef2c transcriptional activity, supporting a physiological role for Mef2c in the retina. In addition, Mef2c appeared to act as a transcriptional repressor of its own expression and the expression of the retina-specific retinal G-protein coupled receptor (Rgr), rhodopsin, and M-opsin genes.
CONCLUSIONS
These findings highlight the early altered regulation of the rod-specific transcriptional network in Rpe65-related disease. They also indicate that Mef2c may act as a novel transcription factor involved in the development and the maintenance of photoreceptor cells.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Ophthalmology |
UniBE Contributor: |
Escher, Pascal |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
0146-0404 |
Publisher: |
Association for Research in Vision and Ophthalmology |
Language: |
English |
Submitter: |
Pascal Escher |
Date Deposited: |
10 Jul 2017 13:35 |
Last Modified: |
05 Dec 2022 15:06 |
Publisher DOI: |
10.1167/iovs.10-6978 |
PubMed ID: |
21715356 |
BORIS DOI: |
10.7892/boris.101783 |
URI: |
https://boris.unibe.ch/id/eprint/101783 |
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