CPSF1 mediates retinal vascular dysfunction in diabetes mellitus via the MAPK/ERK pathway

Jingyi Zhang1, Xi Zhang1, Yuanyuan Zou1

  • 1The Second Department of Ophthalmology, Cangzhou Central Hospital, Cangzhou, Hebei, China.

Insights

This study reveals that CPSF1 is downregulated in diabetic retinopathy (DR). Upregulating CPSF1 in retinal cells alleviates cell damage and dysfunction, suggesting a therapeutic target for DR.

Area of Science:

  • Ophthalmology
  • Molecular Biology
  • Diabetology

Background:

  • Diabetic retinopathy (DR) is a leading cause of vision loss.
  • The molecular mechanisms underlying DR pathogenesis require further elucidation.
  • CPSF1's role in DR has not been previously investigated.

Purpose of the Study:

  • To investigate the expression of CPSF1 in diabetic retinopathy.
  • To explore the molecular mechanism of CPSF1 in regulating retinal vascular cells under high glucose conditions.
  • To determine the therapeutic potential of CPSF1 in DR.

Main Methods:

  • Established a diabetic rat model using streptozotocin (STZ).
  • Utilized high-glucose (HG)-induced human retinal vascular endothelial cells (HRVECs) for in vitro studies.
  • Employed adeno-associated viral vectors for CPSF1 gene delivery.

Main Results:

  • CPSF1 expression was significantly downregulated in DR tissues and HG-treated HRVECs.
  • Adeno-associated viral CPSF1 delivery attenuated retinal histological abnormalities.
  • CPSF1 modulated apoptosis, migration, and vascularization of HRVECs.
  • CPSF1 suppressed MAPK/ERK pathway phosphorylation, mediating retinal vascular dysfunction.

Conclusions:

  • CPSF1 is downregulated in diabetic retinopathy.
  • Upregulated CPSF1 alleviates DR-associated cellular apoptosis and migration.
  • CPSF1 exerts its effects via the MAPK/ERK signaling pathway.
  • CPSF1 represents a potential therapeutic target for diabetic retinopathy.