Caffeine Inhibits Choroidal Neovascularization Through Mitigation of Inflammatory and Angiogenesis Activities
Adenosine receptors (AR) are widely expressed in a variety of tissues including the retina and brain. They are involved in adenosine-mediated immune responses underlying the onset and progression of neurodegenerative diseases. The expression of AR has been previously demonstrated in some retinal cel...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-10-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.737426/full |
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| author | Christine M. Sorenson Christine M. Sorenson Yong-Seok Song Ismail S. Zaitoun Ismail S. Zaitoun Shoujian Wang Barbara A. Hanna Soesiawati R. Darjatmoko Soesiawati R. Darjatmoko Zafer Gurel Debra L. Fisk Colleen M. McDowell Colleen M. McDowell Ryan M. McAdams Nader Sheibani Nader Sheibani Nader Sheibani Nader Sheibani |
| author_facet | Christine M. Sorenson Christine M. Sorenson Yong-Seok Song Ismail S. Zaitoun Ismail S. Zaitoun Shoujian Wang Barbara A. Hanna Soesiawati R. Darjatmoko Soesiawati R. Darjatmoko Zafer Gurel Debra L. Fisk Colleen M. McDowell Colleen M. McDowell Ryan M. McAdams Nader Sheibani Nader Sheibani Nader Sheibani Nader Sheibani |
| author_sort | Christine M. Sorenson |
| collection | DOAJ |
| description | Adenosine receptors (AR) are widely expressed in a variety of tissues including the retina and brain. They are involved in adenosine-mediated immune responses underlying the onset and progression of neurodegenerative diseases. The expression of AR has been previously demonstrated in some retinal cells including endothelial cells and retinal pigment epithelial cells, but their expression in the choroid and choroidal cells remains unknown. Caffeine is a widely consumed AR antagonist that can influence inflammation and vascular cell function. It has established roles in the treatment of neonatal sleep apnea, acute migraine, and post lumbar puncture headache as well as the neurodegenerative diseases such as Parkinson and Alzheimer. More recently, AR antagonism with caffeine has been shown to protect preterm infants from ischemic retinopathy and retinal neovascularization. However, whether caffeine impacts the development and progression of ocular age-related diseases including neovascular age-related macular degermation remains unknown. Here, we examined the expression of AR in retinal and choroidal tissues and cells. We showed that antagonism of AR with caffeine or istradefylline decreased sprouting of thoracic aorta and choroid/retinal pigment epithelium explants in ex vivo cultures, consistent with caffeine’s ability to inhibit endothelial cell migration in culture. In vivo studies also demonstrated the efficacy of caffeine in inhibition of choroidal neovascularization and mononuclear phagocyte recruitment to the laser lesion sites. Istradefylline, a specific AR 2A antagonist, also decreased choroidal neovascularization. Collectively, our studies demonstrate an important role for expression of AR in the choroid whose antagonism mitigate choroidal inflammatory and angiogenesis activities. |
| first_indexed | 2024-12-14T08:39:44Z |
| format | Article |
| id | doaj.art-02459f7142584f92902c60fc09be27df |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-14T08:39:44Z |
| publishDate | 2021-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-02459f7142584f92902c60fc09be27df2022-12-21T23:09:20ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-10-01910.3389/fcell.2021.737426737426Caffeine Inhibits Choroidal Neovascularization Through Mitigation of Inflammatory and Angiogenesis ActivitiesChristine M. Sorenson0Christine M. Sorenson1Yong-Seok Song2Ismail S. Zaitoun3Ismail S. Zaitoun4Shoujian Wang5Barbara A. Hanna6Soesiawati R. Darjatmoko7Soesiawati R. Darjatmoko8Zafer Gurel9Debra L. Fisk10Colleen M. McDowell11Colleen M. McDowell12Ryan M. McAdams13Nader Sheibani14Nader Sheibani15Nader Sheibani16Nader Sheibani17Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI, United StatesMcPherson Eye Research Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI, United StatesDepartment of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI, United StatesMcPherson Eye Research Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI, United StatesDepartment of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI, United StatesDepartment of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI, United StatesDepartment of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI, United StatesMcPherson Eye Research Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI, United StatesDepartment of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI, United StatesDepartment of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI, United StatesDepartment of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI, United StatesMcPherson Eye Research Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI, United StatesDepartment of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI, United StatesDepartment of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI, United StatesMcPherson Eye Research Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI, United StatesDepartment of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI, United StatesDepartment of Cell and Regenerative Biology, University of Wisconsin School of Medicine and Public Health, Madison, WI, United StatesDepartment of Biomedical Engineering, University of Wisconsin School of Medicine and Public Health, Madison, WI, United StatesAdenosine receptors (AR) are widely expressed in a variety of tissues including the retina and brain. They are involved in adenosine-mediated immune responses underlying the onset and progression of neurodegenerative diseases. The expression of AR has been previously demonstrated in some retinal cells including endothelial cells and retinal pigment epithelial cells, but their expression in the choroid and choroidal cells remains unknown. Caffeine is a widely consumed AR antagonist that can influence inflammation and vascular cell function. It has established roles in the treatment of neonatal sleep apnea, acute migraine, and post lumbar puncture headache as well as the neurodegenerative diseases such as Parkinson and Alzheimer. More recently, AR antagonism with caffeine has been shown to protect preterm infants from ischemic retinopathy and retinal neovascularization. However, whether caffeine impacts the development and progression of ocular age-related diseases including neovascular age-related macular degermation remains unknown. Here, we examined the expression of AR in retinal and choroidal tissues and cells. We showed that antagonism of AR with caffeine or istradefylline decreased sprouting of thoracic aorta and choroid/retinal pigment epithelium explants in ex vivo cultures, consistent with caffeine’s ability to inhibit endothelial cell migration in culture. In vivo studies also demonstrated the efficacy of caffeine in inhibition of choroidal neovascularization and mononuclear phagocyte recruitment to the laser lesion sites. Istradefylline, a specific AR 2A antagonist, also decreased choroidal neovascularization. Collectively, our studies demonstrate an important role for expression of AR in the choroid whose antagonism mitigate choroidal inflammatory and angiogenesis activities.https://www.frontiersin.org/articles/10.3389/fcell.2021.737426/fullangiogenesisadenosine receptorsage-related macular degenerationretinal and choroidal endothelial cellschoroidal melanocytes |
| spellingShingle | Christine M. Sorenson Christine M. Sorenson Yong-Seok Song Ismail S. Zaitoun Ismail S. Zaitoun Shoujian Wang Barbara A. Hanna Soesiawati R. Darjatmoko Soesiawati R. Darjatmoko Zafer Gurel Debra L. Fisk Colleen M. McDowell Colleen M. McDowell Ryan M. McAdams Nader Sheibani Nader Sheibani Nader Sheibani Nader Sheibani Caffeine Inhibits Choroidal Neovascularization Through Mitigation of Inflammatory and Angiogenesis Activities Frontiers in Cell and Developmental Biology angiogenesis adenosine receptors age-related macular degeneration retinal and choroidal endothelial cells choroidal melanocytes |
| title | Caffeine Inhibits Choroidal Neovascularization Through Mitigation of Inflammatory and Angiogenesis Activities |
| title_full | Caffeine Inhibits Choroidal Neovascularization Through Mitigation of Inflammatory and Angiogenesis Activities |
| title_fullStr | Caffeine Inhibits Choroidal Neovascularization Through Mitigation of Inflammatory and Angiogenesis Activities |
| title_full_unstemmed | Caffeine Inhibits Choroidal Neovascularization Through Mitigation of Inflammatory and Angiogenesis Activities |
| title_short | Caffeine Inhibits Choroidal Neovascularization Through Mitigation of Inflammatory and Angiogenesis Activities |
| title_sort | caffeine inhibits choroidal neovascularization through mitigation of inflammatory and angiogenesis activities |
| topic | angiogenesis adenosine receptors age-related macular degeneration retinal and choroidal endothelial cells choroidal melanocytes |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2021.737426/full |
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