The cytokine IL-27 reduces inflammation and protects photoreceptors in a mouse model of retinal degeneration
Abstract Background Retinal degenerative diseases are a group of conditions characterized by photoreceptor death and vision loss. Excessive inflammation and microglial activation contribute to the pathology of retinal degenerations and a major focus in the field is identifying more effective anti-in...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2022-09-01
|
| Series: | Journal of Neuroinflammation |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12974-022-02576-x |
| _version_ | 1811273684488290304 |
|---|---|
| author | Andrea Nortey Kimberly Garces Tal Carmy-Bennun Abigail S. Hackam |
| author_facet | Andrea Nortey Kimberly Garces Tal Carmy-Bennun Abigail S. Hackam |
| author_sort | Andrea Nortey |
| collection | DOAJ |
| description | Abstract Background Retinal degenerative diseases are a group of conditions characterized by photoreceptor death and vision loss. Excessive inflammation and microglial activation contribute to the pathology of retinal degenerations and a major focus in the field is identifying more effective anti-inflammatory therapeutic strategies that promote photoreceptor survival. A major challenge to developing anti-inflammatory treatments is to selectively suppress detrimental inflammation while maintaining beneficial inflammatory responses. We recently demonstrated that endogenous levels of the IL-27 cytokine were upregulated in association with an experimental treatment that increased photoreceptor survival. IL-27 is a pleiotropic cytokine that regulates tissue reactions to infection, neuronal disease and tumors by inducing anti-apoptotic and anti-inflammatory genes and suppressing pro-inflammatory genes. IL-27 is neuroprotective in the brain, but its function during retinal degeneration has not been investigated. In this study, we investigated the effect of IL-27 in the rd10 mouse model of inherited photoreceptor degeneration. Methods Male and female rd10 mice were randomly divided into experimental (IL-27) and control (saline) groups and intravitreally injected at age post-natal day (P) 18. Retina function was analyzed by electroretinograms (ERGs), visual acuity by optomotor assay, photoreceptor death by TdT-mediated dUTP nick-end labeling (TUNEL) assay, microglia/macrophage were detected by immunodetection of IBA1 and inflammatory mediators by cytoplex and QPCR analysis. The distribution of IL-27 in the retina was determined by immunohistochemistry on retina cross-sections and primary Muller glia cultures. Results We demonstrate that recombinant IL-27 decreased photoreceptor death, increased retinal function and reduced inflammation in the rd10 mouse model of retinal degeneration. Furthermore, IL-27 injections led to lower levels of the pro-inflammatory proteins Ccl22, IL-18 and IL-12. IL-27 expression was localized to Muller glia and IL-27 receptors to microglia, which are key cell types that regulate photoreceptor survival. Conclusion Our results identify for the first time anti-inflammatory and neuroprotective activities of IL-27 in a genetic model of retinal degeneration. These findings provide new insight into the therapeutic potential of anti-inflammatory cytokines as a treatment for degenerative diseases of the retina. |
| first_indexed | 2024-04-12T23:03:42Z |
| format | Article |
| id | doaj.art-a10163cc9f104537b4ac834508435024 |
| institution | Directory Open Access Journal |
| issn | 1742-2094 |
| language | English |
| last_indexed | 2024-04-12T23:03:42Z |
| publishDate | 2022-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj.art-a10163cc9f104537b4ac8345084350242022-12-22T03:12:59ZengBMCJournal of Neuroinflammation1742-20942022-09-0119111110.1186/s12974-022-02576-xThe cytokine IL-27 reduces inflammation and protects photoreceptors in a mouse model of retinal degenerationAndrea Nortey0Kimberly Garces1Tal Carmy-Bennun2Abigail S. Hackam3Bascom Palmer Eye Institute, University of Miami Miller School of MedicineBascom Palmer Eye Institute, University of Miami Miller School of MedicineBascom Palmer Eye Institute, University of Miami Miller School of MedicineBascom Palmer Eye Institute, University of Miami Miller School of MedicineAbstract Background Retinal degenerative diseases are a group of conditions characterized by photoreceptor death and vision loss. Excessive inflammation and microglial activation contribute to the pathology of retinal degenerations and a major focus in the field is identifying more effective anti-inflammatory therapeutic strategies that promote photoreceptor survival. A major challenge to developing anti-inflammatory treatments is to selectively suppress detrimental inflammation while maintaining beneficial inflammatory responses. We recently demonstrated that endogenous levels of the IL-27 cytokine were upregulated in association with an experimental treatment that increased photoreceptor survival. IL-27 is a pleiotropic cytokine that regulates tissue reactions to infection, neuronal disease and tumors by inducing anti-apoptotic and anti-inflammatory genes and suppressing pro-inflammatory genes. IL-27 is neuroprotective in the brain, but its function during retinal degeneration has not been investigated. In this study, we investigated the effect of IL-27 in the rd10 mouse model of inherited photoreceptor degeneration. Methods Male and female rd10 mice were randomly divided into experimental (IL-27) and control (saline) groups and intravitreally injected at age post-natal day (P) 18. Retina function was analyzed by electroretinograms (ERGs), visual acuity by optomotor assay, photoreceptor death by TdT-mediated dUTP nick-end labeling (TUNEL) assay, microglia/macrophage were detected by immunodetection of IBA1 and inflammatory mediators by cytoplex and QPCR analysis. The distribution of IL-27 in the retina was determined by immunohistochemistry on retina cross-sections and primary Muller glia cultures. Results We demonstrate that recombinant IL-27 decreased photoreceptor death, increased retinal function and reduced inflammation in the rd10 mouse model of retinal degeneration. Furthermore, IL-27 injections led to lower levels of the pro-inflammatory proteins Ccl22, IL-18 and IL-12. IL-27 expression was localized to Muller glia and IL-27 receptors to microglia, which are key cell types that regulate photoreceptor survival. Conclusion Our results identify for the first time anti-inflammatory and neuroprotective activities of IL-27 in a genetic model of retinal degeneration. These findings provide new insight into the therapeutic potential of anti-inflammatory cytokines as a treatment for degenerative diseases of the retina.https://doi.org/10.1186/s12974-022-02576-xCytokinePhotoreceptorsIL-27Retinal degenerationInflammation |
| spellingShingle | Andrea Nortey Kimberly Garces Tal Carmy-Bennun Abigail S. Hackam The cytokine IL-27 reduces inflammation and protects photoreceptors in a mouse model of retinal degeneration Journal of Neuroinflammation Cytokine Photoreceptors IL-27 Retinal degeneration Inflammation |
| title | The cytokine IL-27 reduces inflammation and protects photoreceptors in a mouse model of retinal degeneration |
| title_full | The cytokine IL-27 reduces inflammation and protects photoreceptors in a mouse model of retinal degeneration |
| title_fullStr | The cytokine IL-27 reduces inflammation and protects photoreceptors in a mouse model of retinal degeneration |
| title_full_unstemmed | The cytokine IL-27 reduces inflammation and protects photoreceptors in a mouse model of retinal degeneration |
| title_short | The cytokine IL-27 reduces inflammation and protects photoreceptors in a mouse model of retinal degeneration |
| title_sort | cytokine il 27 reduces inflammation and protects photoreceptors in a mouse model of retinal degeneration |
| topic | Cytokine Photoreceptors IL-27 Retinal degeneration Inflammation |
| url | https://doi.org/10.1186/s12974-022-02576-x |
| work_keys_str_mv | AT andreanortey thecytokineil27reducesinflammationandprotectsphotoreceptorsinamousemodelofretinaldegeneration AT kimberlygarces thecytokineil27reducesinflammationandprotectsphotoreceptorsinamousemodelofretinaldegeneration AT talcarmybennun thecytokineil27reducesinflammationandprotectsphotoreceptorsinamousemodelofretinaldegeneration AT abigailshackam thecytokineil27reducesinflammationandprotectsphotoreceptorsinamousemodelofretinaldegeneration AT andreanortey cytokineil27reducesinflammationandprotectsphotoreceptorsinamousemodelofretinaldegeneration AT kimberlygarces cytokineil27reducesinflammationandprotectsphotoreceptorsinamousemodelofretinaldegeneration AT talcarmybennun cytokineil27reducesinflammationandprotectsphotoreceptorsinamousemodelofretinaldegeneration AT abigailshackam cytokineil27reducesinflammationandprotectsphotoreceptorsinamousemodelofretinaldegeneration |