KIT ligand protects against both light-induced and genetic photoreceptor degeneration
- Wenzhou Medical University, China
- Jinan University, China
Abstract
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.
Data availability
Sequencing data have been deposited in GEO under accession codes 146176.All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for Figure 1-supplment figure 1, Figure 2, Figure 3, Figure 4, Figure 5, Figure 5-fig supplement 1, Figure 8, Figure 9, Figure 9-supplment figure 1.
Article and author information
Author details
Funding
National Natural Science Foundation of China (81800838)
- Huirong Li
National Natural Science Foundation of China (81770946)
- Ling Hou
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All animal experiments were carried out in accordance with the approved guidelines of the Wenzhou Medical University Institutional Animal Care and Use Committee (Permit Number: WZMCOPT-090316).
Reviewing Editor
- Claude Desplan, New York University, United States
Publication history
- Received: September 6, 2019
- Accepted: April 2, 2020
- Accepted Manuscript published: April 3, 2020 (version 1)
- Version of Record published: April 20, 2020 (version 2)
- Version of Record updated: April 27, 2021 (version 3)
Copyright
© 2020, Li et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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KIT ligand protects against both light-induced and genetic photoreceptor degeneration
eLife 9:e51698.
https://doi.org/10.7554/eLife.51698
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