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Impacts of ciliary neurotrophic factor on the retinal transcriptome in a mouse model of photoreceptor degeneration
Ciliary neurotrophic factor (CNTF) has been tested in clinical trials for human retinal degeneration due to its potent neuroprotective effects in various animal models. To decipher CNTF-triggered molecular events in the degenerating retina, we performed high-throughput RNA sequencing analyses using...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7171121/ https://www.ncbi.nlm.nih.gov/pubmed/32313077 http://dx.doi.org/10.1038/s41598-020-63519-1 |
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author | Wang, Yanjie Rhee, Kun-Do Pellegrini, Matteo Yang, Xian-Jie |
author_facet | Wang, Yanjie Rhee, Kun-Do Pellegrini, Matteo Yang, Xian-Jie |
author_sort | Wang, Yanjie |
collection | PubMed |
description | Ciliary neurotrophic factor (CNTF) has been tested in clinical trials for human retinal degeneration due to its potent neuroprotective effects in various animal models. To decipher CNTF-triggered molecular events in the degenerating retina, we performed high-throughput RNA sequencing analyses using the Rds/Prph2 (P216L) transgenic mouse as a preclinical model for retinitis pigmentosa. In the absence of CNTF treatment, transcriptome alterations were detected at the onset of rod degeneration compared with wild type mice, including reduction of key photoreceptor transcription factors Crx, Nrl, and rod phototransduction genes. Short-term CNTF treatments caused further declines of photoreceptor transcription factors accompanied by marked decreases of both rod- and cone-specific gene expression. In addition, CNTF triggered acute elevation of transcripts in the innate immune system and growth factor signaling. These immune responses were sustained after long-term CNTF exposures that also affected neuronal transmission and metabolism. Comparisons of transcriptomes also uncovered common pathways shared with other retinal degeneration models. Cross referencing bulk RNA-seq with single-cell RNA-seq data revealed the CNTF responsive cell types, including Müller glia, rod and cone photoreceptors, and bipolar cells. Together, these results demonstrate the influence of exogenous CNTF on the retinal transcriptome landscape and illuminate likely CNTF impacts in degenerating human retinas. |
format | Online Article Text |
id | pubmed-7171121 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-71711212020-04-23 Impacts of ciliary neurotrophic factor on the retinal transcriptome in a mouse model of photoreceptor degeneration Wang, Yanjie Rhee, Kun-Do Pellegrini, Matteo Yang, Xian-Jie Sci Rep Article Ciliary neurotrophic factor (CNTF) has been tested in clinical trials for human retinal degeneration due to its potent neuroprotective effects in various animal models. To decipher CNTF-triggered molecular events in the degenerating retina, we performed high-throughput RNA sequencing analyses using the Rds/Prph2 (P216L) transgenic mouse as a preclinical model for retinitis pigmentosa. In the absence of CNTF treatment, transcriptome alterations were detected at the onset of rod degeneration compared with wild type mice, including reduction of key photoreceptor transcription factors Crx, Nrl, and rod phototransduction genes. Short-term CNTF treatments caused further declines of photoreceptor transcription factors accompanied by marked decreases of both rod- and cone-specific gene expression. In addition, CNTF triggered acute elevation of transcripts in the innate immune system and growth factor signaling. These immune responses were sustained after long-term CNTF exposures that also affected neuronal transmission and metabolism. Comparisons of transcriptomes also uncovered common pathways shared with other retinal degeneration models. Cross referencing bulk RNA-seq with single-cell RNA-seq data revealed the CNTF responsive cell types, including Müller glia, rod and cone photoreceptors, and bipolar cells. Together, these results demonstrate the influence of exogenous CNTF on the retinal transcriptome landscape and illuminate likely CNTF impacts in degenerating human retinas. Nature Publishing Group UK 2020-04-20 /pmc/articles/PMC7171121/ /pubmed/32313077 http://dx.doi.org/10.1038/s41598-020-63519-1 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Wang, Yanjie Rhee, Kun-Do Pellegrini, Matteo Yang, Xian-Jie Impacts of ciliary neurotrophic factor on the retinal transcriptome in a mouse model of photoreceptor degeneration |
title | Impacts of ciliary neurotrophic factor on the retinal transcriptome in a mouse model of photoreceptor degeneration |
title_full | Impacts of ciliary neurotrophic factor on the retinal transcriptome in a mouse model of photoreceptor degeneration |
title_fullStr | Impacts of ciliary neurotrophic factor on the retinal transcriptome in a mouse model of photoreceptor degeneration |
title_full_unstemmed | Impacts of ciliary neurotrophic factor on the retinal transcriptome in a mouse model of photoreceptor degeneration |
title_short | Impacts of ciliary neurotrophic factor on the retinal transcriptome in a mouse model of photoreceptor degeneration |
title_sort | impacts of ciliary neurotrophic factor on the retinal transcriptome in a mouse model of photoreceptor degeneration |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7171121/ https://www.ncbi.nlm.nih.gov/pubmed/32313077 http://dx.doi.org/10.1038/s41598-020-63519-1 |
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