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

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.