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Necrostatin-1 Protects Photoreceptors from Cell Death and Improves Functional Outcome after Experimental Retinal Detachment
- Source :
- The American Journal of Pathology. 181:1634-1641
- Publication Year :
- 2012
- Publisher :
- Elsevier BV, 2012.
-
Abstract
- Necroptosis is a recently discovered programmed necrosis. Evidence demonstrated the importance of necroptosis in neuronal cell death. Necrostatin-1 is a specific inhibitor of necroptosis. In this study, we investigated the role of necrostatin-1 on photoreceptor survival and functional protection after experimental retinal detachment (RD) in rats. Necrostatin-1/inactive analogue of necrostatin-1 was introduced into the subretinal space at RD induction and 6 hours afterward, respectively. We found that necrostatin-1 attenuated retinal histopathological damage and reduced plasma membrane breakdown (a morphological hallmark of necroptosis) in outer retinal layers. Transmission electron microscopy showed that necrostatin-1 directly protected neurons by inhibiting necroptotic, not apoptotic, cell death. Treatment with necrostatin-1 inhibited the induction of receptor-interacting protein kinase phosphorylation after RD (a biomarker of necroptosis). Finally, electroretinographic recording proved that necrostatin-1 contributed to objective functional improvement after RD. These findings indicate that necrostatin-1 is a promising therapeutic agent that protects photoreceptors from necroptosis and improves functional outcome.
- Subjects :
- Male
Programmed cell death
Cell Membrane Permeability
Indoles
Necroptosis
Biology
Pathology and Forensic Medicine
Rats, Sprague-Dawley
chemistry.chemical_compound
Night vision
Electroretinography
medicine
Animals
Phosphorylation
Protein kinase A
Night Vision
Cell Death
medicine.diagnostic_test
Imidazoles
Retinal Detachment
Retinal
Recovery of Function
Cytoprotection
Rats
Cell biology
chemistry
Apoptosis
Receptor-Interacting Protein Serine-Threonine Kinases
Photoreceptor Cells, Vertebrate
Propidium
Subjects
Details
- ISSN :
- 00029440
- Volume :
- 181
- Database :
- OpenAIRE
- Journal :
- The American Journal of Pathology
- Accession number :
- edsair.doi.dedup.....d41a25bd5356443ec458709a39b874d1