PUBLICATION
The adenosine A (2A) receptor antagonist SCH58261 protects photoreceptors by inhibiting microglial activation and the inflammatory response
- Authors
- Cheng, Y., Cao, P., Geng, C., Chu, X., Li, Y., Cui, J.
- ID
- ZDB-PUB-220924-38
- Date
- 2022
- Source
- International Immunopharmacology 112: 109245 (Journal)
- Registered Authors
- Cui, Jianlin, Li, Yuhao
- Keywords
- Adenosine A (2A) receptor, Light damage, Microglia, Photoreceptor, SCH58261
- MeSH Terms
-
- Animals
- Humans
- Inflammation/drug therapy
- Microglia*
- Receptor, Adenosine A2A
- Retinal Degeneration*/drug therapy
- Zebrafish
- PubMed
- 36150227 Full text @ Int. Immunopharmacol.
Citation
Cheng, Y., Cao, P., Geng, C., Chu, X., Li, Y., Cui, J. (2022) The adenosine A (2A) receptor antagonist SCH58261 protects photoreceptors by inhibiting microglial activation and the inflammatory response. International Immunopharmacology. 112:109245.
Abstract
Photoreceptor degeneration is a principal event in a variety of human retinal diseases. Progressive apoptosis of photoreceptors leads to impaired vision and blindness, for which there is no curative treatment. Adenosine 2A receptors (A2AR) are expressed in microglia. Blockade of A2AR has been shown to protect neurons via suppression of inflammation. However, the therapeutic effects of A2AR antagonists on photoreceptor degeneration have not been characterized. In this study, adult zebrafish were exposed to short term high-intensity light to induce photoreceptor death. SCH58261, a selective A2AR antagonist, was immediately injected into the vitreous body. Photoreceptor degeneration and microglia-induced inflammation were evaluated using immunohistochemistry, quantitative real-time polymerase chain reaction, polarization sensitive optical coherence tomography, and optomotor response. Co-culture of BV2 and 661W cells was used to investigate the interaction between microglia and photoreceptors. The results showed that A2AR was over-expressed during photoreceptor degeneration. Following intraocular SCH58261 injection, microglial activation and release of inflammatory factors were inhibited, and photoreceptor survival increased. Inactivation of microglia prevented apoptosis and autophagy in photoreceptors. Our results showed that SCH58261 intervention at the early stage of photoreceptor degeneration protected photoreceptors through inhibition of the inflammatory response, apoptosis, and autophagy.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping