Conditional Loss of the Exocyst Component Exoc5 in Retinal Pigment Epithelium (RPE) Results in RPE Dysfunction, Photoreceptor Cell Degeneration, and Decreased Visual Function
To characterize the mechanisms by which the highly conserved exocyst trafficking complex regulates eye physiology in zebrafish and mice, we focused on Exoc5 (also known as <i>sec10</i>), a central exocyst component. We analyzed both <i>exoc5</i> zebrafish mutants and retinal...
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MDPI AG
2021-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/10/5083 |
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| author | Bärbel Rohrer Manas R. Biswal Elisabeth Obert Yujing Dang Yanhui Su Xiaofeng Zuo Ben Fogelgren Altaf A. Kondkar Glenn P. Lobo Joshua H. Lipschutz |
| author_facet | Bärbel Rohrer Manas R. Biswal Elisabeth Obert Yujing Dang Yanhui Su Xiaofeng Zuo Ben Fogelgren Altaf A. Kondkar Glenn P. Lobo Joshua H. Lipschutz |
| author_sort | Bärbel Rohrer |
| collection | DOAJ |
| description | To characterize the mechanisms by which the highly conserved exocyst trafficking complex regulates eye physiology in zebrafish and mice, we focused on Exoc5 (also known as <i>sec10</i>), a central exocyst component. We analyzed both <i>exoc5</i> zebrafish mutants and retinal pigmented epithelium (RPE)-specific <i>Exoc5</i> knockout mice. Exoc5 is present in both the non-pigmented epithelium of the ciliary body and in the RPE. In this study, we set out to establish an animal model to study the mechanisms underlying the ocular phenotype and to establish if loss of visual function is induced by postnatal RPE Exoc5-deficiency. <i>Exoc5</i><sup>−/−</sup> zebrafish had smaller eyes, with decreased number of melanocytes in the RPE and shorter photoreceptor outer segments. At 3.5 days post-fertilization, loss of rod and cone opsins were observed in zebrafish <i>exoc5</i> mutants. Mice with postnatal RPE-specific loss of Exoc5 showed retinal thinning associated with compromised visual function and loss of visual photoreceptor pigments. Abnormal levels of RPE65 together with a reduced c-wave amplitude indicate a dysfunctional RPE. The retinal phenotype in <i>Exoc5</i><sup>−/−</sup> mice was present at 20 weeks, but was more pronounced at 27 weeks, indicating progressive disease phenotype. We previously showed that the exocyst is necessary for photoreceptor ciliogenesis and retinal development. Here, we report that <i>exoc5</i> mutant zebrafish and mice with RPE-specific genetic ablation of Exoc5 develop abnormal RPE pigmentation, resulting in retinal cell dystrophy and loss of visual pigments associated with compromised vision. Together, these data suggest that exocyst-mediated signaling in the RPE is required for RPE structure and function, indirectly leading to photoreceptor degeneration. |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T11:32:15Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-f2c95f6f50444756bbc38a94cf0761662023-11-21T19:12:35ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-05-012210508310.3390/ijms22105083Conditional Loss of the Exocyst Component Exoc5 in Retinal Pigment Epithelium (RPE) Results in RPE Dysfunction, Photoreceptor Cell Degeneration, and Decreased Visual FunctionBärbel Rohrer0Manas R. Biswal1Elisabeth Obert2Yujing Dang3Yanhui Su4Xiaofeng Zuo5Ben Fogelgren6Altaf A. Kondkar7Glenn P. Lobo8Joshua H. Lipschutz9Department of Ophthalmology, Medical University of South Carolina, Charleston, SC 29425, USADepartment of Pharmaceutical Sciences, Taneja College of Pharmacy, University of South Florida, Tampa, FL 33612, USADepartment of Ophthalmology, Medical University of South Carolina, Charleston, SC 29425, USADepartment of Medicine, Medical University of South Carolina, Charleston, SC 29425, USADepartment of Medicine, Medical University of South Carolina, Charleston, SC 29425, USADepartment of Medicine, Medical University of South Carolina, Charleston, SC 29425, USADepartment of Anatomy, Biochemistry, and Physiology, University of Hawaii at Manoa, Honolulu, HI 96813, USADepartment of Ophthalmology, College of Medicine, King Saud University, Riyadh 11411, Saudi ArabiaDepartment of Ophthalmology, Medical University of South Carolina, Charleston, SC 29425, USADepartment of Medicine, Medical University of South Carolina, Charleston, SC 29425, USATo characterize the mechanisms by which the highly conserved exocyst trafficking complex regulates eye physiology in zebrafish and mice, we focused on Exoc5 (also known as <i>sec10</i>), a central exocyst component. We analyzed both <i>exoc5</i> zebrafish mutants and retinal pigmented epithelium (RPE)-specific <i>Exoc5</i> knockout mice. Exoc5 is present in both the non-pigmented epithelium of the ciliary body and in the RPE. In this study, we set out to establish an animal model to study the mechanisms underlying the ocular phenotype and to establish if loss of visual function is induced by postnatal RPE Exoc5-deficiency. <i>Exoc5</i><sup>−/−</sup> zebrafish had smaller eyes, with decreased number of melanocytes in the RPE and shorter photoreceptor outer segments. At 3.5 days post-fertilization, loss of rod and cone opsins were observed in zebrafish <i>exoc5</i> mutants. Mice with postnatal RPE-specific loss of Exoc5 showed retinal thinning associated with compromised visual function and loss of visual photoreceptor pigments. Abnormal levels of RPE65 together with a reduced c-wave amplitude indicate a dysfunctional RPE. The retinal phenotype in <i>Exoc5</i><sup>−/−</sup> mice was present at 20 weeks, but was more pronounced at 27 weeks, indicating progressive disease phenotype. We previously showed that the exocyst is necessary for photoreceptor ciliogenesis and retinal development. Here, we report that <i>exoc5</i> mutant zebrafish and mice with RPE-specific genetic ablation of Exoc5 develop abnormal RPE pigmentation, resulting in retinal cell dystrophy and loss of visual pigments associated with compromised vision. Together, these data suggest that exocyst-mediated signaling in the RPE is required for RPE structure and function, indirectly leading to photoreceptor degeneration.https://www.mdpi.com/1422-0067/22/10/5083retinal pigmented epitheliumexocyst complex component 5photoreceptorvisual function |
| spellingShingle | Bärbel Rohrer Manas R. Biswal Elisabeth Obert Yujing Dang Yanhui Su Xiaofeng Zuo Ben Fogelgren Altaf A. Kondkar Glenn P. Lobo Joshua H. Lipschutz Conditional Loss of the Exocyst Component Exoc5 in Retinal Pigment Epithelium (RPE) Results in RPE Dysfunction, Photoreceptor Cell Degeneration, and Decreased Visual Function International Journal of Molecular Sciences retinal pigmented epithelium exocyst complex component 5 photoreceptor visual function |
| title | Conditional Loss of the Exocyst Component Exoc5 in Retinal Pigment Epithelium (RPE) Results in RPE Dysfunction, Photoreceptor Cell Degeneration, and Decreased Visual Function |
| title_full | Conditional Loss of the Exocyst Component Exoc5 in Retinal Pigment Epithelium (RPE) Results in RPE Dysfunction, Photoreceptor Cell Degeneration, and Decreased Visual Function |
| title_fullStr | Conditional Loss of the Exocyst Component Exoc5 in Retinal Pigment Epithelium (RPE) Results in RPE Dysfunction, Photoreceptor Cell Degeneration, and Decreased Visual Function |
| title_full_unstemmed | Conditional Loss of the Exocyst Component Exoc5 in Retinal Pigment Epithelium (RPE) Results in RPE Dysfunction, Photoreceptor Cell Degeneration, and Decreased Visual Function |
| title_short | Conditional Loss of the Exocyst Component Exoc5 in Retinal Pigment Epithelium (RPE) Results in RPE Dysfunction, Photoreceptor Cell Degeneration, and Decreased Visual Function |
| title_sort | conditional loss of the exocyst component exoc5 in retinal pigment epithelium rpe results in rpe dysfunction photoreceptor cell degeneration and decreased visual function |
| topic | retinal pigmented epithelium exocyst complex component 5 photoreceptor visual function |
| url | https://www.mdpi.com/1422-0067/22/10/5083 |
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