Essential roles of mitochondrial biogenesis regulator Nrf1 in retinal development and homeostasis
| Autor: | Chai An Mao, William H. Klein, Takae Kiyama, Zhenlin Ju, Jing Wang, Ching-Kang Chen, Shinako Takada, Steven W. Wang, Ping Pan |
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| Rok vydání: | 2018 |
| Předmět: |
Retinal progenitor cell
Retinal Ganglion Cells 0301 basic medicine Neurogenesis Mice Transgenic Neural degeneration lcsh:Geriatrics Mitochondrion Biology Retinal ganglion lcsh:RC346-429 Retina Nrf1 03 medical and health sciences Cellular and Molecular Neuroscience Mitochondrial biogenesis Photoreceptor degeneration medicine Animals Homeostasis Optic atrophy Retinal ganglion cell NRF1 Molecular Biology lcsh:Neurology. Diseases of the nervous system Mice Knockout Organelle Biogenesis Nuclear Respiratory Factor 1 Stem Cells Mitochondria Cell biology lcsh:RC952-954.6 030104 developmental biology medicine.anatomical_structure sense organs Neurology (clinical) Neural development Research Article |
| Zdroj: | Molecular Neurodegeneration Molecular Neurodegeneration, Vol 13, Iss 1, Pp 1-23 (2018) |
| ISSN: | 1750-1326 |
| Popis: | Background Mitochondrial dysfunction has been implicated in the pathologies of a number of retinal degenerative diseases in both the outer and inner retina. In the outer retina, photoreceptors are particularly vulnerable to mutations affecting mitochondrial function due to their high energy demand and sensitivity to oxidative stress. However, it is unclear how defective mitochondrial biogenesis affects neural development and contributes to neural degeneration. In this report, we investigated the in vivo function of nuclear respiratory factor 1 (Nrf1), a major transcriptional regulator of mitochondrial biogenesis in both proliferating retinal progenitor cells (RPCs) and postmitotic rod photoreceptor cells (PRs). Methods We used mouse genetic techniques to generate RPC-specific and rod PR-specific Nrf1 conditional knockout mouse models. We then applied a comprehensive set of tools, including histopathological and molecular analyses, RNA-seq, and electroretinography on these mouse lines to study Nrf1-regulated genes and Nrf1’s roles in both developing retinas and differentiated rod PRs. For all comparisons between genotypes, a two-tailed two-sample student’s t-test was used. Results were considered significant when P |
| Databáze: | OpenAIRE |
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