Receptor-Interacting Protein Kinase-3 Expression Impacts Ocular Vascular Development and Pathological Neovascularization
Functional cell death pathways are essential for normal ocular vascular development and tissue homeostasis. As our understanding of necrosis-based cell death pathways has expanded, the inclusion of regulated forms, including necroptosis, ferroptosis, and oxytosis, has occurred. Although the existenc...
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2024-12-01
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| author | Yong-Seok Song Shoujian Wang SunYoung Park Barbara Hanna Kelsey J. Johnson Soesiawati R. Darjatmoko Mohammad Ali Saghiri Ali Mohammad Saghiri Bo Liu Christine M. Sorenson Nader Sheibani |
| author_facet | Yong-Seok Song Shoujian Wang SunYoung Park Barbara Hanna Kelsey J. Johnson Soesiawati R. Darjatmoko Mohammad Ali Saghiri Ali Mohammad Saghiri Bo Liu Christine M. Sorenson Nader Sheibani |
| author_sort | Yong-Seok Song |
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| description | Functional cell death pathways are essential for normal ocular vascular development and tissue homeostasis. As our understanding of necrosis-based cell death pathways has expanded, the inclusion of regulated forms, including necroptosis, ferroptosis, and oxytosis, has occurred. Although the existence of these pathways is well described, our understanding of their role during vascular development and pathological neovascularization is very limited. Here, we examined the role of receptor-interacting protein kinase-3 (Ripk3), a key regulator of necroptosis, in postnatal retinal vascularization and retinal and choroidal neovascularization under pathological conditions. Postnatal vascularization of the retinal superficial layer in the absence of Ripk3 (<i>Ripk3</i><sup>−/−</sup>) was not significantly different from wild-type mice. However, we noted decreased retinal endothelial cells and pericyte numbers at 3 weeks of age when the formation of the retinal primary vascular plexus was complete. In contrast, choroidal and retinal neovascularization following laser treatment and oxygen-induced ischemic retinopathy increased in the absence of Ripk3 expression, respectively. In addition, the inhibition of RIPK1/3 activity suppressed choroidal neovascularization. Thus, Ripk3 expression and/or activity may have unique roles during normal and pathological ocular vascularization through its interactions with Caspase 8 and modulation of cell death processes. |
| format | Article |
| id | doaj-art-bbbdfe1808d24ccdac938f37bbd311dc |
| institution | OA Journals |
| issn | 2073-4409 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | MDPI AG |
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| series | Cells |
| spelling | doaj-art-bbbdfe1808d24ccdac938f37bbd311dc2025-08-20T02:00:43ZengMDPI AGCells2073-44092024-12-011324210910.3390/cells13242109Receptor-Interacting Protein Kinase-3 Expression Impacts Ocular Vascular Development and Pathological NeovascularizationYong-Seok Song0Shoujian Wang1SunYoung Park2Barbara Hanna3Kelsey J. Johnson4Soesiawati R. Darjatmoko5Mohammad Ali Saghiri6Ali Mohammad Saghiri7Bo Liu8Christine M. Sorenson9Nader Sheibani10Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USADepartment of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USADepartment of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USADepartment of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USADepartment of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USADepartment of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USADepartment of Restorative Dentistry, Rutgers School of Dental Medicine, Newark, NJ 07103, USADepartment of Computer Science, William Paterson University, Wayne, NJ 07470, USADepartment of Cell and Regenerative Biology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USAMcPherson Eye Research Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USADepartment of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USAFunctional cell death pathways are essential for normal ocular vascular development and tissue homeostasis. As our understanding of necrosis-based cell death pathways has expanded, the inclusion of regulated forms, including necroptosis, ferroptosis, and oxytosis, has occurred. Although the existence of these pathways is well described, our understanding of their role during vascular development and pathological neovascularization is very limited. Here, we examined the role of receptor-interacting protein kinase-3 (Ripk3), a key regulator of necroptosis, in postnatal retinal vascularization and retinal and choroidal neovascularization under pathological conditions. Postnatal vascularization of the retinal superficial layer in the absence of Ripk3 (<i>Ripk3</i><sup>−/−</sup>) was not significantly different from wild-type mice. However, we noted decreased retinal endothelial cells and pericyte numbers at 3 weeks of age when the formation of the retinal primary vascular plexus was complete. In contrast, choroidal and retinal neovascularization following laser treatment and oxygen-induced ischemic retinopathy increased in the absence of Ripk3 expression, respectively. In addition, the inhibition of RIPK1/3 activity suppressed choroidal neovascularization. Thus, Ripk3 expression and/or activity may have unique roles during normal and pathological ocular vascularization through its interactions with Caspase 8 and modulation of cell death processes.https://www.mdpi.com/2073-4409/13/24/2109oxygen-induced ischemic retinopathychoroidal neovascularizationnecroptosisRIPK-proteinsretinal vascularization |
| spellingShingle | Yong-Seok Song Shoujian Wang SunYoung Park Barbara Hanna Kelsey J. Johnson Soesiawati R. Darjatmoko Mohammad Ali Saghiri Ali Mohammad Saghiri Bo Liu Christine M. Sorenson Nader Sheibani Receptor-Interacting Protein Kinase-3 Expression Impacts Ocular Vascular Development and Pathological Neovascularization Cells oxygen-induced ischemic retinopathy choroidal neovascularization necroptosis RIPK-proteins retinal vascularization |
| title | Receptor-Interacting Protein Kinase-3 Expression Impacts Ocular Vascular Development and Pathological Neovascularization |
| title_full | Receptor-Interacting Protein Kinase-3 Expression Impacts Ocular Vascular Development and Pathological Neovascularization |
| title_fullStr | Receptor-Interacting Protein Kinase-3 Expression Impacts Ocular Vascular Development and Pathological Neovascularization |
| title_full_unstemmed | Receptor-Interacting Protein Kinase-3 Expression Impacts Ocular Vascular Development and Pathological Neovascularization |
| title_short | Receptor-Interacting Protein Kinase-3 Expression Impacts Ocular Vascular Development and Pathological Neovascularization |
| title_sort | receptor interacting protein kinase 3 expression impacts ocular vascular development and pathological neovascularization |
| topic | oxygen-induced ischemic retinopathy choroidal neovascularization necroptosis RIPK-proteins retinal vascularization |
| url | https://www.mdpi.com/2073-4409/13/24/2109 |
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