Quantitative Proteomics of Human Retinal Pigment Epithelium Reveals Key Regulators for the Pathogenesis of Age-Related Macular Degeneration

Shichen Shen, Becky Kapphahn, Ming Zhang, Shuo Qian, Sandra R. Montezuma, Peng Shang, Deborah A Ferrington, Jun Qu

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Age-related macular degeneration (AMD) is the leading cause of blindness in elderly people, with limited treatment options available for most patients. AMD involves the death of retinal pigment epithelium (RPE) and photoreceptor cells, with mitochondria dysfunction being a critical early event. In the current study, we utilized our unique resource of human donor RPE graded for AMD presence and severity to investigate proteome-wide dysregulation involved in early AMD. Organelle-enriched fractions of RPE were isolated from donors with early AMD (n = 45) and healthy age-matched controls (n = 32) and were analyzed by UHR-IonStar, an integrated proteomics platform enabling reliable and in-depth proteomic quantification in large cohorts. A total of 5941 proteins were quantified with excellent analytical reproducibility, and with further informatics analysis, many biological functions and pathways were found to be significantly dysregulated in donor RPE samples with early AMD. Several of these directly pinpointed changes in mitochondrial functions, e.g., translation, ATP metabolic process, lipid homeostasis, and oxidative stress. These novel findings highlighted the value of our proteomics investigation by allowing a better understanding of the molecular mechanisms underlying early AMD onset and facilitating both treatment development and biomarker discovery.

Original languageEnglish (US)
Article number3252
JournalInternational journal of molecular sciences
Volume24
Issue number4
DOIs
StatePublished - Feb 2023

Bibliographical note

Funding Information:
This research was funded by the National Institutes of Health/National Eye Institute, grant numbers EY028554, EY026012, and EY034669, Wallen Neuroscience Discovery Fund, the Helen Lindsay Foundation, an anonymous donor for AMD research, and the Stephen J Ryan—Arnold and Mabel Beckman Foundation Endowed Presidential Chair.

Publisher Copyright:
© 2023 by the authors.

Keywords

  • age-related macular degeneration
  • IonStar
  • mass spectrometry
  • mitochondria dysfunction
  • quantitative proteomics
  • retinal pigment epithelium

PubMed: MeSH publication types

  • Journal Article

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