P2X7 Is Involved in the Mouse Retinal Degeneration via the Coordinated Actions in Different Retinal Cell Types

Ponarulselvam Sekar, George Hsiao, Yuan Shen Chen, Wan Wan Lin, Chi Ming Chan

研究成果: 雜誌貢獻文章同行評審

2 引文 斯高帕斯(Scopus)


Adenosine triphosphate (ATP) released from dying cells with high concentrations is sensed as a danger signal by the P2X7 receptor. Sodium iodate (NaIO3) is an oxidative toxic agent, and its retinal toxicity has been used as the model of dry age-related macular degeneration (AMD). In this study, we used NaIO3-treated mice and cultured retinal cells, including BV-2 microglia, 661W photoreceptors, rMC1 Müller cells and ARPE-19 retinal epithelial cells, to understand the pathological action of P2X7 in retinal degeneration. We found that NaIO3 can significantly decrease the photoreceptor function by reducing a-wave and b-wave amplitudes in electroretinogram (ERG) analysis. Optical coherence tomography (OCT) analysis revealed the degeneration of retinal epithelium and ganglion cell layers. Interestingly, P2X7−/− mice were protected from the NaIO3-induced retinopathy and inflammatory NLRP3, IL-1β and IL-6 gene expression in the retina. Hematoxylin and eosin staining indicated that the retinal epithelium was less deteriorated in P2X7−/− mice compared to the WT group. Although P2X7 was barely detected in 661W, rMC1 and ARPE-19 cells, its gene and protein levels can be increased after NaIO3 treatment, leading to a synergistic cytotoxicity of BzATP [2′(3′)-O-(4-benzoylbenzoyl)adenosine-5′-triphosphate tri(triethyleneammonium)salt] and NaIO3 administration in ARPE-19 cells. In conclusion, the paracrine action of the ATP/P2X7 axis via cell–cell communication is involved in NaIO3-induced retinal injury. Our results show that P2X7 antagonist might be a potential therapy in inflammation-related retinal degeneration.
出版狀態已發佈 - 1月 2023

ASJC Scopus subject areas

  • 食品科學
  • 生理學
  • 生物化學
  • 分子生物學
  • 臨床生物化學
  • 細胞生物學


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