July 2019
Volume 60, Issue 9
Free
ARVO Annual Meeting Abstract  |   July 2019
Cyclooxygenase-1 (COX-1) modulates neuroinflammation in the rd10 mouse model of retinitis pigmentosa
Author Affiliations & Notes
  • Bin Lin
    School of Optometry, The Hong Kong Polytechnic University, Kowloon, Hong Kong
  • Wei Yang
    School of Optometry, The Hong Kong Polytechnic University, Kowloon, Hong Kong
  • Meng Cheng
    School of Optometry, The Hong Kong Polytechnic University, Kowloon, Hong Kong
  • Rong Li
    School of Optometry, The Hong Kong Polytechnic University, Kowloon, Hong Kong
  • Footnotes
    Commercial Relationships   Bin Lin, None; Wei Yang, None; Meng Cheng, None; Rong Li, None
  • Footnotes
    Support  This work was supported by the Health and Medical Research Fund (HMRF) of Hong Kong Food and Health Bureau (Project no: 01120856)
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 430. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Bin Lin, Wei Yang, Meng Cheng, Rong Li; Cyclooxygenase-1 (COX-1) modulates neuroinflammation in the rd10 mouse model of retinitis pigmentosa. Invest. Ophthalmol. Vis. Sci. 2019;60(9):430.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose : Retinitis pigmentosa (RP) is a heterogeneous group of inherited disorders caused by a number of gene mutations that result in initial death of rods followed by cone photoreceptors. The mechanisms underlying photoreceptor death are not yet completely understood. Neuroinflammation is reported to be involved in RP progression. However, the mechanisms that trigger neuroinflammation remain unclear. Here, we investigated the role of COX-1, a key enzyme in the conversion of arachidonic acid to prostaglandins, in modulating neuroinflammation in rd10 mice.

Methods : To address the role of COX-1, we treated rd10 mice with the highly selective COX-1 inhibitor SC-560 or backcrossed COX-1 knockout mice onto rd10 background and generated a COX-1-/-/rd10 mouse line. We investigate the effect of COX-1 inhibition or deletion on the status of microglia activation and photoreceptor survival using a combination of immunocytochemistry, RT-PCR, western blot analysis, and a series of simple visual tests. To identify the key downstream mediator of COX-1 activity, we administered rd10 mice with an antagonist that blocks the prostaglandin E2 receptor (EP2).

Results : Both pharmacological inhibition with SC-560 and genetic deletion of COX-1 reduced microgliosis, resulted in a decrease in the production of inflammatory mediators including PGE2, TNF-α, IL-1β and NF-κB, and enhanced photoreceptor cell survival, retinal function and visual performance in rd10 mice. These data supported a pathological role of COX-1 in RP. Moreover, we identified that the EP2 receptor was a key downstream effector of COX-1 neurotoxicityin rd10 mice.

Conclusions : We demonstrated that COX-1-mediated inflammation contributed to photoreceptor degeneration in rd10 mice, and that the COX-1/PGE2/EP2 signaling pathway played an important role in mediating neuroinflammatory responses and disease progression in rd10 mice. The therapeutic approaches centered around COX-1 inhibition might be a potential strategy for treating RP patients.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×