June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Non-caveolar Caveolin-1 in Müller glia regulate retinal innate immune responses
Author Affiliations & Notes
  • Eric N Enyong
    Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States
    Ophthalmology, Dean McGee Eye Institute, Oklahoma City, Oklahoma, United States
  • Jami M Gurley
    Ophthalmology, Dean McGee Eye Institute, Oklahoma City, Oklahoma, United States
  • Martin-Paul Gameli Agbaga
    Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States
    Ophthalmology, Dean McGee Eye Institute, Oklahoma City, Oklahoma, United States
  • Michael H Elliott
    Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States
    Ophthalmology, Dean McGee Eye Institute, Oklahoma City, Oklahoma, United States
  • Footnotes
    Commercial Relationships   Eric Enyong None; Jami Gurley None; Martin-Paul Agbaga None; Michael Elliott None
  • Footnotes
    Support  NIH Grants R01EY019494 and NEI Core Grant P30EY021725: Presbyterian Health Foundation Research Scholar Award
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 4116 – F0353. doi:
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    • Get Citation

      Eric N Enyong, Jami M Gurley, Martin-Paul Gameli Agbaga, Michael H Elliott; Non-caveolar Caveolin-1 in Müller glia regulate retinal innate immune responses. Invest. Ophthalmol. Vis. Sci. 2022;63(7):4116 – F0353.

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

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Abstract

Purpose : The role of Caveolin-1 (Cav1), the signature protein of caveolae, in regulation of innate immune response seems controversial, since Cav1 can either promote or suppress immune response in a cell-context manner. We speculate that caveolar and non-caveolar localization of Cav1 in different cells accounts for this paradoxical immune regulatory role. Here, we show that non-caveolar Cav1 in Müller glia enhance lipopolysaccharide (LPS)-induced interleukin-6 (IL-6) response, which can be blunted by either Cav1 silencing or sequestration into caveolae

Methods : To investigate the role of non-caveolar Cav1 in immune regulation, we either silenced Cav1 using Cav1-shRNA, or sequestered Cav1 into caveolae by expressing Cavin1/PTRF in MIO-M1 Müller glia and measured IL-6 response in tissue culture media by ELISA, with or without LPS stimulation. We used quantitative proteomics to identify immune-related pathways enriched in Cav1 immunoprecipitates from control and Cavin1/PTRF-expressing MIO-M1 Müller glia. Additionally we performed immunocytochemistry staining of MIO-M1 Müller glia using fluorescently labeled phalloidin to evaluate changes in filamentous actin (F-actin) when Cavin1/PTRF is expressed

Results : LPS stimulation of MIO-M1 Müller glia significantly increased IL-6 secretion into tissue culture media. Surprisingly, both Cav1 silencing or Cavin1/PTRF expression in MIO-M1 Müller glia significantly suppressed LPS-induced IL-6 response. Analysis of mass spectrometry data revealed significant differential association of different proteins with Cav1 when Cavin1/PTRF is expressed. Interestingly, we identified 18 genes in 11 of the 30 most enriched pathways for proteins with significantly increased association with Cav1 that were associated with immune-related pathways. These were distributed among seven distinct immune-related gene ontology (GO) functional categories including neutrophil activation, neutrophil degranulation, immune effector process and immune response. Furthermore, expression of Cavin1/PTRF in MIO-M1 Müller glia significantly reduced F-actin staining intensity

Conclusions : Our results suggest that non-caveolar Cav1 in MIO-M1 Müller glia enhance LPS-induced innate immune response. Expression of Cavin1/PTRF sequesters Cav1 into caveolae, which alters critical pathways involved in immune regulation, with remodeling of actin cytoskeleton as a potential mechanism

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

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