RBM15 promotes hyperglycemia-induced retinal endothelial cell injury by regulating FOXO3 stability via m6A

Yang Yu1, Yuqing Ren2, Su Dong3

  • 1Department of Ophthalmology, Children's Hospital of Nanjing Medical University, 72 Guangzhou Road, Nanjing, 210008, P.R. China. ykyyyy2018@163.com.

Insights

Researchers identified the RBM15/m6A/FOXO3 pathway as crucial in diabetic retinopathy (DR). Targeting RBM15 may offer a new treatment for DR by protecting retinal endothelial cells from high glucose damage.

Area of Science:

  • Ophthalmology
  • Molecular Biology
  • Endocrinology

Background:

  • Diabetic retinopathy (DR) is a major cause of vision loss.
  • N6-methyladenosine (m6A) modifications are increasingly recognized as regulators in DR.
  • The role of the m6A writer RBM15 in high glucose-induced retinal endothelial cell injury is unclear.

Purpose of the Study:

  • To investigate the function of RBM15 in high glucose-induced retinal endothelial cell injury.
  • To elucidate the molecular mechanism by which RBM15 affects diabetic retinopathy.

Main Methods:

  • Examined RBM15 expression in diabetic mouse retinas and high glucose-challenged endothelial cells (ECs).
  • Utilized RBM15 knockdown in vitro and in vivo models.
  • Assessed apoptosis, autophagy, retinal thinning, capillary formation, and vascular leakage.
  • Investigated the m6A-dependent modulation of FOXO3 mRNA stability.

Main Results:

  • RBM15 was upregulated in diabetic retinas and high glucose-treated ECs.
  • RBM15 knockdown reduced EC apoptosis and rescued autophagy deficiency.
  • Downregulating RBM15 attenuated DR hallmarks in diabetic mice.
  • RBM15 regulated EC apoptosis and autophagy via m6A-dependent control of FOXO3 mRNA stability.

Conclusions:

  • The RBM15/m6A/FOXO3 pathway is a key regulator of high glucose-induced retinal microvascular dysfunction.
  • RBM15 emerges as a potential therapeutic target for diabetic retinopathy.