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KIT ligand protects against both light-induced and genetic photoreceptor degeneration

Photoreceptor degeneration is a major cause of blindness and a considerable health burden during aging but effective therapeutic or preventive strategies have not so far become readily available. Here, we show in mouse models that signaling through the tyrosine kinase receptor KIT protects photorece...

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Autores principales: Li, Huirong, Lian, Lili, Liu, Bo, Chen, Yu, Yang, Jinglei, Jian, Shuhui, Zhou, Jiajia, Xu, Ying, Ma, Xiaoyin, Qu, Jia, Hou, Ling
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7170656/
https://www.ncbi.nlm.nih.gov/pubmed/32242818
http://dx.doi.org/10.7554/eLife.51698
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author Li, Huirong
Lian, Lili
Liu, Bo
Chen, Yu
Yang, Jinglei
Jian, Shuhui
Zhou, Jiajia
Xu, Ying
Ma, Xiaoyin
Qu, Jia
Hou, Ling
author_facet Li, Huirong
Lian, Lili
Liu, Bo
Chen, Yu
Yang, Jinglei
Jian, Shuhui
Zhou, Jiajia
Xu, Ying
Ma, Xiaoyin
Qu, Jia
Hou, Ling
author_sort Li, Huirong
collection PubMed
description Photoreceptor degeneration is a major cause of blindness and a considerable health burden during aging but effective therapeutic or preventive strategies have not so far become readily available. Here, we show in mouse models that signaling through the tyrosine kinase receptor KIT protects photoreceptor cells against both light-induced and inherited retinal degeneration. Upon light damage, photoreceptor cells upregulate Kit ligand (KITL) and activate KIT signaling, which in turn induces nuclear accumulation of the transcription factor NRF2 and stimulates the expression of the antioxidant gene Hmox1. Conversely, a viable Kit mutation promotes light-induced photoreceptor damage, which is reversed by experimental expression of Hmox1. Furthermore, overexpression of KITL from a viral AAV8 vector prevents photoreceptor cell death and partially restores retinal function after light damage or in genetic models of human retinitis pigmentosa. Hence, application of KITL may provide a novel therapeutic avenue for prevention or treatment of retinal degenerative diseases.
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spelling pubmed-71706562020-04-22 KIT ligand protects against both light-induced and genetic photoreceptor degeneration Li, Huirong Lian, Lili Liu, Bo Chen, Yu Yang, Jinglei Jian, Shuhui Zhou, Jiajia Xu, Ying Ma, Xiaoyin Qu, Jia Hou, Ling eLife Neuroscience Photoreceptor degeneration is a major cause of blindness and a considerable health burden during aging but effective therapeutic or preventive strategies have not so far become readily available. Here, we show in mouse models that signaling through the tyrosine kinase receptor KIT protects photoreceptor cells against both light-induced and inherited retinal degeneration. Upon light damage, photoreceptor cells upregulate Kit ligand (KITL) and activate KIT signaling, which in turn induces nuclear accumulation of the transcription factor NRF2 and stimulates the expression of the antioxidant gene Hmox1. Conversely, a viable Kit mutation promotes light-induced photoreceptor damage, which is reversed by experimental expression of Hmox1. Furthermore, overexpression of KITL from a viral AAV8 vector prevents photoreceptor cell death and partially restores retinal function after light damage or in genetic models of human retinitis pigmentosa. Hence, application of KITL may provide a novel therapeutic avenue for prevention or treatment of retinal degenerative diseases. eLife Sciences Publications, Ltd 2020-04-03 /pmc/articles/PMC7170656/ /pubmed/32242818 http://dx.doi.org/10.7554/eLife.51698 Text en © 2020, Li et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Neuroscience
Li, Huirong
Lian, Lili
Liu, Bo
Chen, Yu
Yang, Jinglei
Jian, Shuhui
Zhou, Jiajia
Xu, Ying
Ma, Xiaoyin
Qu, Jia
Hou, Ling
KIT ligand protects against both light-induced and genetic photoreceptor degeneration
title KIT ligand protects against both light-induced and genetic photoreceptor degeneration
title_full KIT ligand protects against both light-induced and genetic photoreceptor degeneration
title_fullStr KIT ligand protects against both light-induced and genetic photoreceptor degeneration
title_full_unstemmed KIT ligand protects against both light-induced and genetic photoreceptor degeneration
title_short KIT ligand protects against both light-induced and genetic photoreceptor degeneration
title_sort kit ligand protects against both light-induced and genetic photoreceptor degeneration
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7170656/
https://www.ncbi.nlm.nih.gov/pubmed/32242818
http://dx.doi.org/10.7554/eLife.51698
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