June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Immunomodulatory Outcomes of Astroglial p65 Deletion in Experimental Mouse Glaucoma
Author Affiliations & Notes
  • Gulgun Tezel
    Ophthalmology, Columbia University Irving Medical Center, New York, New York, United States
  • Xiangjun Yang
    Ophthalmology, Columbia University Irving Medical Center, New York, New York, United States
  • Qun Zeng
    Ophthalmology, Columbia University Irving Medical Center, 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 2022, Vol.63, 919 – A0388. doi:
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    • Get Citation

      Gulgun Tezel, Xiangjun Yang, Qun Zeng; Immunomodulatory Outcomes of Astroglial p65 Deletion in Experimental Mouse Glaucoma. Invest. Ophthalmol. Vis. Sci. 2022;63(7):919 – A0388.

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

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Abstract

Purpose : Recent studies of IκKβ deletion in astroglia showed an essential role of NF-κB for the regulation of neurodegenerative inflammation in glaucoma that besides astroglia responses, astroglial NF-κB can shape microglia responses by regulating the astroglia-microglia crosstalk. This study sought a temporal analysis of the overall impacts of astroglial p65 deletion on neuroinflammation in experimental mouse glaucoma.

Methods : Bead occlusion-induced ocular hypertension was modeled in mice with conditional p65 deletion in astroglia (crossbreds of p65f/f and GFAP-cre/ERT2) and p65f/f controls. Through an ocular hypertensive period of 12-weeks, cytokines/chemokines were profiled in the retina, optic nerve, and vitreous samples using multiplex immunoassays. Transgenic effects on glial morphological responses were determined in retinal whole mounts and optic nerve sections by immunolabeling-based quantitative parameters (such as the coverage/intensity of GFAP or Iba1 immunolabeling). Transgenic effects on neurodegeneration were analyzed by counting RGCs and axons.

Results : Pro-inflammatory molecules exhibited a noticeable reduction in samples from ocular hypertensive GFAP/p65 mice, accompanied by protected RGC and axon survival (P < 0.001) compared to ocular hypertensive p65f/f controls. The pro-inflammatory cytokines presenting decreased titers with astroglial p65 deletion included transcriptional targets for NF-κB, such as ILs, TNF-α, IFN-γ (P < 0.01). The coverage and intensity of GFAP immunolabeling were significantly decreased with astroglial p65 deletion in ocular hypertensive eyes (P < 0.001). Similar to recent observations, microglia also exhibited a lessened morphological response to ocular hypertension with p65 deletion in astroglia. A characteristic shift of microglia from ramified morphology to reactive morphology with ocular hypertension was less prominent, and the Iba1 coverage and intensity were over 30% less (P = 0.002, P = 0.01, respectively) in ocular hypertensive GFAP/p65 mice than ocular hypertensive p65f/f controls.

Conclusions : These findings further support the importance of astroglial NF-κB as a transgenic treatment target to reduce neurodegenerative inflammation in glaucoma. The ability to detect immunomodulatory responses by vitreous cytokine profiling may also be promising to guide future translational studies for predictive, prognostic, and therapeutic testing for personalized patient care.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

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