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Author Spotlight: THP-1 Macrophage Response to LPS/ATP — Unveiling the Pyroptosis, Apoptosis, and Necroptosis Spectrum
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Author Spotlight: THP-1 Macrophage Response to LPS/ATP — Unveiling the Pyroptosis, Apoptosis, and Necroptosis Spectrum

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PYGM downregulates necroptosis signaling to attenuate sodium iodate-induced RPE cell degeneration

Yaqi Cheng1, Simin Gu1, Huan Yu2

  • 1Department of Ophthalmology, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, China.

Cellular Signalling
|November 3, 2025
PubMed
Abstract

Insights

Pyruvate kinase M (PYGM) gene expression protects against cell death in models of age-related macular degeneration (AMD). Upregulating PYGM may offer a novel therapeutic strategy for dry AMD vision loss.

Area of Science:

  • Ophthalmology
  • Cellular Biology
  • Molecular Medicine

Background:

  • Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in older adults.
  • Current treatments for dry AMD are limited, highlighting the need for new therapeutic targets.
  • Necroptosis, a programmed form of cell death, is increasingly implicated in AMD pathogenesis.

Purpose of the Study:

  • To investigate the mechanisms driving abnormal necroptosis in age-related macular degeneration (AMD).
  • To identify key genes regulating necroptosis in retinal pigment epithelium (RPE) cells relevant to dry AMD.

Main Methods:

  • Established in vitro and in vivo models of RPE degeneration using sodium iodate (SI) to mimic dry AMD.
  • Analyzed necroptosis markers (RIPK1, RIPK3, MLKL) and performed RNA-sequencing on mouse retinas.
  • Integrated mouse data with human AMD microarray data (GSE29801) to identify regulatory genes.
  • Validated gene function through in vitro and in vivo overexpression studies.

Main Results:

  • Necroptosis markers were significantly upregulated in SI-treated RPE cells and mouse retinas.
  • Reduced expression of the Pyruvate kinase M (PYGM) gene was identified as a key regulator of necroptosis in AMD models.
  • Overexpression of PYGM ameliorated sodium iodate-induced RPE degeneration in both cellular and animal models.

Conclusions:

  • PYGM plays a crucial role in attenuating necroptosis within cellular and animal models of dry AMD.
  • PYGM represents a promising novel therapeutic target for developing treatments for age-related macular degeneration.
Keywords:
Age-related macular degenerationNecroptosisPYGM

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