June 2020
Volume 61, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2020
TAK1 mediates inflammatory responses in the rd10 mouse model of retinitis pigmentosa
Author Affiliations & Notes
  • Wei Yang
    The Hong Kong Polytechnic University, Hong Kong, China
  • Jing Zhang
    The Hong Kong Polytechnic University, Hong Kong, China
  • Bin Lin
    The Hong Kong Polytechnic University, Hong Kong, China
  • Footnotes
    Commercial Relationships   Wei Yang, None; Jing Zhang, None; Bin Lin, None
  • Footnotes
    Support  HK university grant committee
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 681. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Wei Yang, Jing Zhang, Bin Lin; TAK1 mediates inflammatory responses in the rd10 mouse model of retinitis pigmentosa. Invest. Ophthalmol. Vis. Sci. 2020;61(7):681.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : Retinitis Pigmentosa (RP) is a group of neurodegenerative diseases that are characterized by the gradual death of retinal photoreceptors, leading to partial or complete blindness. To date, no effective treatment for RP is available. Neuroinflammation is reported to contribute to retinal degeneration in RP. However, the mechanisms underlying neuroinflammation in RP is still not clear. TAK1 is involved in regulating the production of pro-inflammatory cytokines. Microglia-specific TAK1 has been shown to be pivotal for the pathogenesis of autoimmune inflammation of the central nervous system. Here, we investigated the role of TAK1 in inflammatory responses and photoreceptor death in rd10 mice.

Methods : We initially examined the expression of TAK1 in the rd10 mouse retina using a combination of western blot analysis and immunocytochemistry. To inhibit TAK1, we treated rd10 mice with 5z-7-oxozeaenol (oxo), a selective TAK1 inhibitor, at a dose of 10mg/kg. We then assessed microglia activation and photoreceptor death following oxo treatment. To knock out Tak1 specifically from microglia, we backcrossed Tak1 floxed mice (Tak1fl/fl) and Cx3cr1CreER mice with rd10 background mice to generate a new rd10:Cx3cr1CreER/+:Tak1fl/fl mouse line and treated the resulting mice with tamoxifen (TAM) for 5 consecutive days starting from three different time points (P10, P13 and P16) and then assessed microglia activation and photoreceptor death.

Results : We found that TAK1 protein level was elevated in the rd10 retina compared with C57BL/6J control and TAK1 had a relatively higher expression in microglia than other types of cells. TAK1 inhibition by oxo had a suppressing effect on microglia activation and a protective effect on photoreceptors in the rd10 retina. After administration of TAM to specifically knock out Tak1 from microglia, we observed protective effects on photoreceptors for all three different treatment time points. However, we found that the TAM treatment starting from P10 achieved the best protective effect. Interestingly, we also observed that microglia-specific Tak1 knockout caused apoptosis in microglia, leading to a decrease in the number of microglia in the rd10 retina.

Conclusions : We demonstrated that TAK1 was involved in mediating microgliosis and photoreceptor death in rd10 mice. Our findings suggest that TAK1 might represent a novel therapeutic target for treating chronic inflammation in RP.

This is a 2020 ARVO Annual Meeting abstract.

×
×

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.

×