腺苷A2A受体拮抗剂SCH58261通过抑制小胶质细胞活化和炎症反应保护感光细胞

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 (A 2A R) are expressed in microglia. Blockade of A 2A R has been shown to protect neurons via suppression of inflammation. However, the therapeutic effects of A 2A R 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 A 2A R 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 A 2A R 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.