Cyclooxygenase-1 mediates neuroinflammation and neurotoxicity in a mouse model of retinitis pigmentosa

Wei Yang, Guoyin Xiong, Bin Lin

Research output: Journal article publicationJournal articleAcademic researchpeer-review

1 Citation (Scopus)

Abstract

Background: Retinitis pigmentosa (RP) is a group of inherited eye disorders with progressive degeneration of photoreceptors in the retina, ultimately leading to partial or complete blindness. The mechanisms underlying photoreceptor degeneration are not yet completely understood. Neuroinflammation is reported to play a pathological role in RP. However, the mechanisms that trigger neuroinflammation remain largely unknown. To address this question, we investigated the role of cyclooxygenase-1 (COX-1), a key enzyme in the conversion of arachidonic acid to proinflammatory prostaglandins, in the rd10 mouse model of RP. Methods: We backcrossed COX-1 knockout mice (COX-1 −/−) onto the rd10 mouse model of RP and investigated the impact of COX-1 deletion on neuroinflammation in the resulting COX-1 −/−/rd10 mouse line, using a combination of immunocytochemistry, flow cytometry, qPCR, ELISA, and a series of simple visual tests. Results: We found that genetic ablation or pharmacological inhibition of COX-1 alleviated neuroinflammation and subsequently preserved retinal photoreceptor and function and visual performance in rd10 mice. Moreover, we observed that the pharmacological inhibition of the prostaglandin E2 (PGE2) EP2 receptors largely replicated the beneficial effects of COX-1 deletion, suggesting that EP2 receptor was a critical downstream effector of COX-1-mediated neurotoxicity in rd10 mice. Conclusion: Our data suggest that the COX-1/PGE2/EP2 signaling pathway was partly responsible for significantly increased neuroinflammation and disease progression in rd10 mice, and that EP2 receptor could be targeted therapeutically to block the pathological activity of COX-1 without inducing any potential side effects in treating RP patients.

Original languageEnglish
Article number306
JournalJournal of Neuroinflammation
Volume17
Issue number1
DOIs
Publication statusPublished - 15 Oct 2020

Keywords

  • COX-1
  • EP2 receptor
  • Neuroinflammation
  • Photoreceptors
  • rd10 mice

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology
  • Neurology
  • Cellular and Molecular Neuroscience

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