June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
NF-κB-regulated Cross-talk between Astroglia and Microglia for Neuroinflammation in Experimental Glaucoma
Author Affiliations & Notes
  • Gulgun Tezel
    Ophthalmology, Columbia University, New York, New York, United States
  • Xiangjun Yang
    Ophthalmology, Columbia University, New York, New York, United States
  • Qun Zeng
    Ophthalmology, Columbia University, New York, New York, United States
  • Footnotes
    Commercial Relationships   Gulgun Tezel, None; Xiangjun Yang, None; Qun Zeng, None
  • Footnotes
    Support  NIH Grants R01 EY028153, P30 EY019007, and RPB
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 2351. doi:
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    • Get Citation

      Gulgun Tezel, Xiangjun Yang, Qun Zeng; NF-κB-regulated Cross-talk between Astroglia and Microglia for Neuroinflammation in Experimental Glaucoma. Invest. Ophthalmol. Vis. Sci. 2021;62(8):2351.

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

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Abstract

Purpose : Astroglia and microglia play synchronic/complementary roles during neuroinflammation in glaucoma; however, how they interplay and regulate each other’s phenotype and immune functions is not fully understood. To improve the understanding of astroglia-microglia intersignaling for neuroinflammation in experimental glaucoma, this study analyzed microglia responses to astroglial NF-κB inhibition.

Methods : Ocular hypertension was induced by anterior chamber microbead injections in mice with conditional deletion of p65 in astroglia (crossbreds of p65f/f and GFAP-cre/ERT2) and controls (p65f/f), and astroglia and microglia responses were analyzed through a 12-weeks period. Morphological responses were determined in retinal whole mounts and optic nerve sections by analyzing the intensity and coverage of immunolabeling for specific markers (GFAP or Iba1). Inflammatory responses, and A1/A2 and M1/M2 phenotypes, were evaluated by cytokine/chemokine profiling in isolated astroglia and microglia samples and immunolabeling of retina and optic nerve tissues.

Results : Besides decreased inflammatory activity of p65-deleted astroglia, a prominent decrease was detectable in microglia responses.The morphological response of microglia to ocular hypertension (a shift from ramified morphology to reactive morphology) was less prominent, and the intensity and coverage of Iba1 immunolabeling were over 30% less in ocular hypertensive eyes of GFAP/p65 mice than ocular hypertensive p65f/f controls (P = 0.001, P = 0.01, respectively). In addition, similar to p65-deleted astroglia (that were C3- with lower titers of NF-κB-regulated pro-inflammatory cytokines, such as ILs, TNF-α, IFN-γ), the pro-inflammatory cytokine response of microglia was significantly lower in ocular hypertensive GFAP/p65 mice than ocular hypertensive p65f/f controls (P < 0.02). The reduced microglial response to experimental glaucoma should not be related to decreased neuron injury in GFAP/p65 mice, since parallel studies of RGC-protective treatments did not detect a similar response.

Conclusions : These findings support the importance of astroglia-derived factors to shape microglia responses during glaucomatous neurodegeneration. Astroglial NF-κB-regulated cytokines/chemokines appear to critically modulate direct communication, and the amplifying relay effects, between astroglia and microglia during neuroinflammation in experimental glaucoma.

This is a 2021 ARVO Annual Meeting abstract.

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