Inflammasome Activation in Retinal Pigment Epithelium from Human Donors with Age-Related Macular Degeneration

Mara C. Ebeling, Cody R. Fisher, Rebecca J. Kapphahn, Madilyn R. Stahl, Shichen Shen, Jun Qu, Sandra R. Montezuma, Deborah A. Ferrington

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Age-related macular degeneration (AMD), the leading cause of blindness in the elderly, is characterized by the death of retinal pigment epithelium (RPE) and photoreceptors. One of the risk factors associated with developing AMD is the single nucleotide polymorphism (SNP) found within the gene encoding complement factor H (CFH). Part of the innate immune system, CFH inhibits alternative complement pathway activation. Multi-protein complexes called inflammasomes also play a role in the innate immune response. Previous studies reported that inflammasome activation may contribute to AMD pathology. In this study, we used primary human adult RPE cell cultures from multiple donors, with and without AMD, that were genotyped for the Y402H CFH risk allele. We found complement and inflammasome-related genes and proteins at basal levels in RPE tissue and cell cultures. Additionally, treatment with rotenone, bafilomycin A, and ATP led to inflammasome activation. Overall, the response to priming and activation was similar, irrespective of disease state or CFH genotype. While these data show that the inflammasome is present and active in RPE, our results suggest that inflammasome activation may not contribute to early AMD pathology.

Original languageEnglish (US)
Article number2075
JournalCells
Volume11
Issue number13
DOIs
StatePublished - Jul 1 2022

Bibliographical note

Funding Information:
Funding: This research was funded by the National Institutes of Health (NIH) National Eye Institute; R01EY026012 and R01EY028554 (to D.A.F.), F31-EY031558 (to C.R.F.), T32-EY025187 (to C.R.F.), the NIH National Institute on Aging (NIA) T32-AG029796 (to C.R.F.), Diana Jacobs Kalman/AFAR Scholarships for Research in the Biology of Aging (to C.R.F.), VitreoRetinal Surgery Foundation Fellowship (to C.R.F.); the Elaine and Robert Larson Endowed Vision Chair (to D.A.F.); Winston and Maxine Wallin Neuroscience Discovery Fund Award (to D.A.F.), an anonymous benefactor for Macular Degeneration Research; and the Lindsay Family Foundation. None of the funding agencies had a role in the study design, in the collection, analysis and interpretation of data, in writing the manuscript, or in the decision to submit the manuscript for publication.

Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • age-related macular degeneration
  • complement factor H
  • inflammasome
  • inflammation
  • retinal pigment epithelium

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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