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mm9_circ_014683 regulates microglia polarization through canonical NFκB signaling pathway in diabetic retinopathy

Tingting Chen1, Congyao Wang1, Wenhui Zhu1

  • 1Department of Ophthalmology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China.

Cellular Signalling
|February 28, 2024
PubMed

Insights

Circular RNAs regulate microglia polarization in diabetic retinopathy (DR). This study identifies a key circRNA, mm9_circ_014683, that influences M1/M2 polarization via the NFκB pathway, offering potential therapeutic targets for DR.

Area of Science:

  • Ophthalmology
  • Immunology
  • Molecular Biology

Background:

  • Diabetic retinopathy (DR) causes significant vision loss, with retinal microglia-mediated inflammation being a key factor.
  • Previous research indicated M1 microglial polarization contributes to DR inflammation, but the underlying mechanisms require further elucidation.
  • Circular RNAs (circRNAs) are emerging as crucial regulators in cellular processes.

Purpose of the Study:

  • To investigate the role of circRNAs in high glucose-induced microglial activation.
  • To identify specific circRNAs involved in microglial polarization in the context of DR.
  • To explore the molecular mechanisms by which identified circRNAs regulate microglial function and their relevance to DR pathogenesis.

Main Methods:

  • Differential circRNA expression profiling in BV2 mouse microglia exposed to high glucose.
  • Functional assays to assess the impact of circRNA mm9_circ_014683 on microglial proliferation, apoptosis, and polarization (M1/M2).
  • Gene expression analysis and pathway enrichment (NFκB signaling) in circRNA-knockdown cells; in vivo validation in diabetic mouse models.

Main Results:

  • 347 differentially expressed circRNAs were identified in glucose-treated BV2 cells, with mm9_circ_014683 being significantly upregulated.
  • Manipulation of mm9_circ_014683 levels modulated M1/M2 microglial polarization without affecting proliferation or apoptosis.
  • mm9_circ_014683 was found to positively regulate the canonical NFκB signaling pathway and was highly expressed in retinal microglia of diabetic mice.

Conclusions:

  • The circRNA mm9_circ_014683 plays a critical role in regulating microglial polarization in diabetic retinopathy.
  • This regulation occurs through the canonical NFκB signaling pathway.
  • mm9_circ_014683 represents a potential therapeutic target for managing DR-associated inflammation and vision loss.
Keywords:
Diabetic retinopathyMicroglia polarizationNFκB signaling pathwaycircRNA

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