Targeting the cochlin/SFRP1/CaMKII axis in the ocular posterior pole prevents the progression of nonpathologic myopia
Abstract Myopia is a major public health issue. However, interventional modalities for nonpathologic myopia are limited due to its complicated pathogenesis and the lack of precise targets. Here, we show that in guinea pig form-deprived myopia (FDM) and lens-induced myopia (LIM) models, the early ini...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-08-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-023-05267-2 |
| _version_ | 1797557155476275200 |
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| author | Chao Geng Siyi Liu Jindan Wang Sennan Wang Weiran Zhang Hua Rong Yunshan Cao Shuqing Wang Zhiqing Li Yan Zhang |
| author_facet | Chao Geng Siyi Liu Jindan Wang Sennan Wang Weiran Zhang Hua Rong Yunshan Cao Shuqing Wang Zhiqing Li Yan Zhang |
| author_sort | Chao Geng |
| collection | DOAJ |
| description | Abstract Myopia is a major public health issue. However, interventional modalities for nonpathologic myopia are limited due to its complicated pathogenesis and the lack of precise targets. Here, we show that in guinea pig form-deprived myopia (FDM) and lens-induced myopia (LIM) models, the early initiation, phenotypic correlation, and stable maintenance of cochlin protein upregulation at the interface between retinal photoreceptors and retinal pigment epithelium (RPE) is identified by a proteomic analysis of ocular posterior pole tissues. Then, a microarray analysis reveals that cochlin upregulates the expression of the secreted frizzled-related protein 1 (SFRP1) gene in human RPE cells. Moreover, SFRP-1 elevates the intracellular Ca2+ concentration and activates Ca2+/calmodulin-dependent protein kinase II (CaMKII) signaling in a simian choroidal vascular endothelial cell line, and elicits vascular endothelial cell dysfunction. Furthermore, genetic knockdown of the cochlin gene and pharmacological blockade of SFRP1 abrogates the reduced choroidal blood perfusion and prevents myopia progression in the FDM model. Collectively, this study identifies a novel signaling axis that may involve cochlin in the retina, SFRP1 in the RPE, and CaMKII in choroidal vascular endothelial cells and contribute to the pathogenesis of nonpathologic myopia, implicating the potential of cochlin and SFRP1 as myopia interventional targets. |
| first_indexed | 2024-03-10T17:12:14Z |
| format | Article |
| id | doaj.art-96e1164527ce4b37afa5e86fc8b369dd |
| institution | Directory Open Access Journal |
| issn | 2399-3642 |
| language | English |
| last_indexed | 2024-03-10T17:12:14Z |
| publishDate | 2023-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj.art-96e1164527ce4b37afa5e86fc8b369dd2023-11-20T10:36:34ZengNature PortfolioCommunications Biology2399-36422023-08-016111910.1038/s42003-023-05267-2Targeting the cochlin/SFRP1/CaMKII axis in the ocular posterior pole prevents the progression of nonpathologic myopiaChao Geng0Siyi Liu1Jindan Wang2Sennan Wang3Weiran Zhang4Hua Rong5Yunshan Cao6Shuqing Wang7Zhiqing Li8Yan Zhang9Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye HospitalTianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye HospitalTianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye HospitalTianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye HospitalTianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye HospitalTianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye HospitalDepartment of Cardiology, Gansu Provincial Hospital, Lanzhou UniversitySchool of Pharmacy, Tianjin Medical UniversityTianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye HospitalTianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye HospitalAbstract Myopia is a major public health issue. However, interventional modalities for nonpathologic myopia are limited due to its complicated pathogenesis and the lack of precise targets. Here, we show that in guinea pig form-deprived myopia (FDM) and lens-induced myopia (LIM) models, the early initiation, phenotypic correlation, and stable maintenance of cochlin protein upregulation at the interface between retinal photoreceptors and retinal pigment epithelium (RPE) is identified by a proteomic analysis of ocular posterior pole tissues. Then, a microarray analysis reveals that cochlin upregulates the expression of the secreted frizzled-related protein 1 (SFRP1) gene in human RPE cells. Moreover, SFRP-1 elevates the intracellular Ca2+ concentration and activates Ca2+/calmodulin-dependent protein kinase II (CaMKII) signaling in a simian choroidal vascular endothelial cell line, and elicits vascular endothelial cell dysfunction. Furthermore, genetic knockdown of the cochlin gene and pharmacological blockade of SFRP1 abrogates the reduced choroidal blood perfusion and prevents myopia progression in the FDM model. Collectively, this study identifies a novel signaling axis that may involve cochlin in the retina, SFRP1 in the RPE, and CaMKII in choroidal vascular endothelial cells and contribute to the pathogenesis of nonpathologic myopia, implicating the potential of cochlin and SFRP1 as myopia interventional targets.https://doi.org/10.1038/s42003-023-05267-2 |
| spellingShingle | Chao Geng Siyi Liu Jindan Wang Sennan Wang Weiran Zhang Hua Rong Yunshan Cao Shuqing Wang Zhiqing Li Yan Zhang Targeting the cochlin/SFRP1/CaMKII axis in the ocular posterior pole prevents the progression of nonpathologic myopia Communications Biology |
| title | Targeting the cochlin/SFRP1/CaMKII axis in the ocular posterior pole prevents the progression of nonpathologic myopia |
| title_full | Targeting the cochlin/SFRP1/CaMKII axis in the ocular posterior pole prevents the progression of nonpathologic myopia |
| title_fullStr | Targeting the cochlin/SFRP1/CaMKII axis in the ocular posterior pole prevents the progression of nonpathologic myopia |
| title_full_unstemmed | Targeting the cochlin/SFRP1/CaMKII axis in the ocular posterior pole prevents the progression of nonpathologic myopia |
| title_short | Targeting the cochlin/SFRP1/CaMKII axis in the ocular posterior pole prevents the progression of nonpathologic myopia |
| title_sort | targeting the cochlin sfrp1 camkii axis in the ocular posterior pole prevents the progression of nonpathologic myopia |
| url | https://doi.org/10.1038/s42003-023-05267-2 |
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