The DOI matches its Crossref record; 16 of the 16 references it cites were found in a registry or an index.
Receptor interacting protein kinase mediates necrotic cone but not rod cell death in a mouse model of inherited degeneration
Open accessAbstract
Retinitis pigmentosa comprises a group of inherited retinal photoreceptor degenerations that lead to progressive loss of vision. Although in most cases rods, but not cones, harbor the deleterious gene mutations, cones do die in this disease, usually after the main phase of rod cell loss. Rod photoreceptor death is characterized by apoptotic features. In contrast, the mechanisms and features of subsequent nonautonomous cone cell death remain largely unknown. In this study, we show that receptor-interacting protein (RIP) kinase mediates necrotic cone cell death in rd10 mice, a mouse model of retinitis pigmentosa caused by a mutation in a rod-specific gene. The expression of RIP3, a key regulator of programmed necrosis, was elevated in rd10 mouse retinas in the phase of cone but not rod degeneration. Although rd10 mice lacking Rip3 developed comparable rod degeneration to control rd10 mice, they displayed a significant preservation of cone cells. Ultrastructural analysis of rd10 mouse retinas revealed that a substantial fraction of dying cones exhibited necrotic morphology, which was rescued by Rip3 deficiency. Additionally, pharmacologic treatment with a RIP kinase inhibitor attenuated histological and functional deficits of cones in rd10 mice. Thus, necrotic mechanisms involving RIP kinase are crucial in cone cell death in inherited retinal degeneration, suggesting the RIP kinase pathway as a potential target to protect cone-mediated central and peripheral vision loss in patients with retinitis pigementosa.
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Necroptosis in development, inflammation and disease
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Necroptosis in health and diseases
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Metadata
- Authors
- Murakami, Y., Matsumoto, H., Roh, M., Suzuki, J., Hisatomi, T., Ikeda, Y., Miller, J. W., & Vavvas, D. G.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2012-08-20
- Volume
- 109
- Issue
- 36
- Pages
- 14598-14603
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2120539953
- Cited by
- 171
- References
- 16
- FWCI
- 5.92
- Type
- journal article
- Language
- en
- Open access
- green
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- Murakami, Y., Matsumoto, H., Roh, M., Suzuki, J., Hisatomi, T., Ikeda, Y., Miller, J. W., & Vavvas, D. G. (2012). Receptor interacting protein kinase mediates necrotic cone but not rod cell death in a mouse model of inherited degeneration. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.1206937109
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