Mural Serum Response Factor (SRF) Deficiency Provides Insights into Retinal Vascular Functionality and Development
Serum response factor (SRF) controls the expression of muscle contraction and motility genes in mural cells (MCs) of the vasculature. In the retina, MC-SRF is important for correct angiogenesis during development and the continuing maintenance of the vascular tone. The purpose of this study was to p...
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MDPI AG
2023-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/16/12597 |
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| author | Alexander Günter Vithiyanjali Sothilingam Michael M. Orlich Alfred Nordheim Mathias W. Seeliger Regine Mühlfriedel |
| author_facet | Alexander Günter Vithiyanjali Sothilingam Michael M. Orlich Alfred Nordheim Mathias W. Seeliger Regine Mühlfriedel |
| author_sort | Alexander Günter |
| collection | DOAJ |
| description | Serum response factor (SRF) controls the expression of muscle contraction and motility genes in mural cells (MCs) of the vasculature. In the retina, MC-SRF is important for correct angiogenesis during development and the continuing maintenance of the vascular tone. The purpose of this study was to provide further insights into the effects of MC SRF deficiency on the vasculature and function of the mature retina in <i>Srf<sup>iMCKO</sup></i> mice that carry a MC-specific deletion of <i>Srf</i>. Retinal morphology and vascular integrity were analyzed in vivo via scanning laser ophthalmoscopy (SLO), angiography, and optical coherence tomography (OCT). Retinal function was evaluated with full-field electroretinography (ERG). We found that retinal blood vessels of these mutants exhibited different degrees of morphological and functional alterations. With increasing severity, we found vascular bulging, the formation of arteriovenous (AV) anastomoses, and ultimately, a retinal detachment (RD). The associated irregular retinal blood pressure and flow distribution eventually induced hypoxia, indicated by a negative ERG waveform shape. Further, the high frequency of interocular differences in the phenotype of individual <i>Srf<sup>iMCKO</sup></i> mice points to a secondary nature of these developments far downstream of the genetic defect and rather dependent on the local retinal context. |
| first_indexed | 2024-03-10T23:53:07Z |
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| id | doaj.art-2276a48de7104bbb88e87c8c8d1d0709 |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T23:53:07Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-2276a48de7104bbb88e87c8c8d1d07092023-11-19T01:25:40ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-08-0124161259710.3390/ijms241612597Mural Serum Response Factor (SRF) Deficiency Provides Insights into Retinal Vascular Functionality and DevelopmentAlexander Günter0Vithiyanjali Sothilingam1Michael M. Orlich2Alfred Nordheim3Mathias W. Seeliger4Regine Mühlfriedel5Division of Ocular Neurodegeneration, Institute for Ophthalmic Research, University of Tübingen, 72076 Tübingen, GermanyDivision of Ocular Neurodegeneration, Institute for Ophthalmic Research, University of Tübingen, 72076 Tübingen, GermanyRudbeck Laboratory, Department of Immunology, Genetics and Pathology, Uppsala University, 75185 Uppsala, SwedenDepartment of Molecular Biology, Interfaculty Institute of Cell Biology, University of Tübingen, 72076 Tübingen, GermanyDivision of Ocular Neurodegeneration, Institute for Ophthalmic Research, University of Tübingen, 72076 Tübingen, GermanyDivision of Ocular Neurodegeneration, Institute for Ophthalmic Research, University of Tübingen, 72076 Tübingen, GermanySerum response factor (SRF) controls the expression of muscle contraction and motility genes in mural cells (MCs) of the vasculature. In the retina, MC-SRF is important for correct angiogenesis during development and the continuing maintenance of the vascular tone. The purpose of this study was to provide further insights into the effects of MC SRF deficiency on the vasculature and function of the mature retina in <i>Srf<sup>iMCKO</sup></i> mice that carry a MC-specific deletion of <i>Srf</i>. Retinal morphology and vascular integrity were analyzed in vivo via scanning laser ophthalmoscopy (SLO), angiography, and optical coherence tomography (OCT). Retinal function was evaluated with full-field electroretinography (ERG). We found that retinal blood vessels of these mutants exhibited different degrees of morphological and functional alterations. With increasing severity, we found vascular bulging, the formation of arteriovenous (AV) anastomoses, and ultimately, a retinal detachment (RD). The associated irregular retinal blood pressure and flow distribution eventually induced hypoxia, indicated by a negative ERG waveform shape. Further, the high frequency of interocular differences in the phenotype of individual <i>Srf<sup>iMCKO</sup></i> mice points to a secondary nature of these developments far downstream of the genetic defect and rather dependent on the local retinal context.https://www.mdpi.com/1422-0067/24/16/12597serum response factormural cellsretinal ischemiamurine disease modelsvascular smooth-muscle cellsretinal imaging |
| spellingShingle | Alexander Günter Vithiyanjali Sothilingam Michael M. Orlich Alfred Nordheim Mathias W. Seeliger Regine Mühlfriedel Mural Serum Response Factor (SRF) Deficiency Provides Insights into Retinal Vascular Functionality and Development International Journal of Molecular Sciences serum response factor mural cells retinal ischemia murine disease models vascular smooth-muscle cells retinal imaging |
| title | Mural Serum Response Factor (SRF) Deficiency Provides Insights into Retinal Vascular Functionality and Development |
| title_full | Mural Serum Response Factor (SRF) Deficiency Provides Insights into Retinal Vascular Functionality and Development |
| title_fullStr | Mural Serum Response Factor (SRF) Deficiency Provides Insights into Retinal Vascular Functionality and Development |
| title_full_unstemmed | Mural Serum Response Factor (SRF) Deficiency Provides Insights into Retinal Vascular Functionality and Development |
| title_short | Mural Serum Response Factor (SRF) Deficiency Provides Insights into Retinal Vascular Functionality and Development |
| title_sort | mural serum response factor srf deficiency provides insights into retinal vascular functionality and development |
| topic | serum response factor mural cells retinal ischemia murine disease models vascular smooth-muscle cells retinal imaging |
| url | https://www.mdpi.com/1422-0067/24/16/12597 |
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