Regulation of distinct caspase-8 functions in retinal ganglion cells and astroglia in experimental glaucoma
Retinal ganglion cells (RGCs) expanding from the retina to the brain are primary victims of neurodegeneration in glaucoma, a leading cause of blindness; however, the neighboring astroglia survive the glaucoma-related stress and promote neuroinflammation. In light of diverse functions of caspase-8 in...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-03-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996121000073 |
| _version_ | 1818869948086222848 |
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| author | Xiangjun Yang Qun Zeng Gülgün Tezel |
| author_facet | Xiangjun Yang Qun Zeng Gülgün Tezel |
| author_sort | Xiangjun Yang |
| collection | DOAJ |
| description | Retinal ganglion cells (RGCs) expanding from the retina to the brain are primary victims of neurodegeneration in glaucoma, a leading cause of blindness; however, the neighboring astroglia survive the glaucoma-related stress and promote neuroinflammation. In light of diverse functions of caspase-8 in apoptosis, cell survival, and inflammation, this study investigated the importance of caspase-8 in different fates of glaucomatous RGCs and astroglia using two experimental approaches in parallel. In the first approach, cell type-specific responses of RGCs and astroglia to a caspase-8 cleavage-inhibiting pharmacological treatment were studied in rat eyes with or without experimentally induced glaucoma. The second approach utilized an experimental model of glaucoma in mice in which astroglial caspase-8 was conditionally deleted by cre/lox. Findings of these experiments revealed cell type-specific distinct processes that regulate caspase-8 functions in experimental glaucoma, which are involved in inducing the apoptosis of RGCs and promoting the survival and inflammatory responses of astroglia. Deletion of caspase-8 in astroglia protected RGCs against glia-driven inflammatory injury, while the inhibition of caspase-8 cleavage inhibited apoptosis in RGCs themselves. Various caspase-8 functions impacting both RGC apoptosis and astroglia-driven neuroinflammation may suggest the multi-target potential of caspase-8 regulation to provide neuroprotection and immunomodulation in glaucoma. |
| first_indexed | 2024-12-19T11:59:14Z |
| format | Article |
| id | doaj.art-0961ecbc61a74ddab7a5f81fa9775667 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-19T11:59:14Z |
| publishDate | 2021-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-0961ecbc61a74ddab7a5f81fa97756672022-12-21T20:22:32ZengElsevierNeurobiology of Disease1095-953X2021-03-01150105258Regulation of distinct caspase-8 functions in retinal ganglion cells and astroglia in experimental glaucomaXiangjun Yang0Qun Zeng1Gülgün Tezel2Department of Ophthalmology, Vagelos College of Physicians and Surgeons, Columbia University, Edward S. Harkness Eye Institute, 635 West 165th Street, New York, NY 10032, United States of AmericaDepartment of Ophthalmology, Vagelos College of Physicians and Surgeons, Columbia University, Edward S. Harkness Eye Institute, 635 West 165th Street, New York, NY 10032, United States of AmericaCorresponding author at: Edward S. Harkness Eye Institute, 635 W 165th St, Box 102, New York, NY 10032, United States of America.; Department of Ophthalmology, Vagelos College of Physicians and Surgeons, Columbia University, Edward S. Harkness Eye Institute, 635 West 165th Street, New York, NY 10032, United States of AmericaRetinal ganglion cells (RGCs) expanding from the retina to the brain are primary victims of neurodegeneration in glaucoma, a leading cause of blindness; however, the neighboring astroglia survive the glaucoma-related stress and promote neuroinflammation. In light of diverse functions of caspase-8 in apoptosis, cell survival, and inflammation, this study investigated the importance of caspase-8 in different fates of glaucomatous RGCs and astroglia using two experimental approaches in parallel. In the first approach, cell type-specific responses of RGCs and astroglia to a caspase-8 cleavage-inhibiting pharmacological treatment were studied in rat eyes with or without experimentally induced glaucoma. The second approach utilized an experimental model of glaucoma in mice in which astroglial caspase-8 was conditionally deleted by cre/lox. Findings of these experiments revealed cell type-specific distinct processes that regulate caspase-8 functions in experimental glaucoma, which are involved in inducing the apoptosis of RGCs and promoting the survival and inflammatory responses of astroglia. Deletion of caspase-8 in astroglia protected RGCs against glia-driven inflammatory injury, while the inhibition of caspase-8 cleavage inhibited apoptosis in RGCs themselves. Various caspase-8 functions impacting both RGC apoptosis and astroglia-driven neuroinflammation may suggest the multi-target potential of caspase-8 regulation to provide neuroprotection and immunomodulation in glaucoma.http://www.sciencedirect.com/science/article/pii/S0969996121000073AstrogliaCaspase-8GlaucomaNeurodegenerationNeuroinflammation |
| spellingShingle | Xiangjun Yang Qun Zeng Gülgün Tezel Regulation of distinct caspase-8 functions in retinal ganglion cells and astroglia in experimental glaucoma Neurobiology of Disease Astroglia Caspase-8 Glaucoma Neurodegeneration Neuroinflammation |
| title | Regulation of distinct caspase-8 functions in retinal ganglion cells and astroglia in experimental glaucoma |
| title_full | Regulation of distinct caspase-8 functions in retinal ganglion cells and astroglia in experimental glaucoma |
| title_fullStr | Regulation of distinct caspase-8 functions in retinal ganglion cells and astroglia in experimental glaucoma |
| title_full_unstemmed | Regulation of distinct caspase-8 functions in retinal ganglion cells and astroglia in experimental glaucoma |
| title_short | Regulation of distinct caspase-8 functions in retinal ganglion cells and astroglia in experimental glaucoma |
| title_sort | regulation of distinct caspase 8 functions in retinal ganglion cells and astroglia in experimental glaucoma |
| topic | Astroglia Caspase-8 Glaucoma Neurodegeneration Neuroinflammation |
| url | http://www.sciencedirect.com/science/article/pii/S0969996121000073 |
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