Targeting endothelial glycolytic reprogramming by tsRNA-1599 for ocular anti-angiogenesis therapy

Area of Science:

• Ophthalmology
• Molecular Biology
• Cell Biology

Background:

• Current ocular angiogenesis treatments targeting VEGF have limitations.
• Novel therapeutic targets for neovascular eye diseases are needed.

Purpose of the Study:

• Investigate the role of tsRNA-1599 in ocular angiogenesis.
• Elucidate the underlying molecular mechanisms of tsRNA-1599-mediated angiogenesis.

Main Methods:

• Utilized in vitro endothelial cell assays (CCK-8, EdU, transwell, matrigel).
• Employed in vivo models: STZ-induced diabetes, laser-induced choroidal neovascularization, oxygen-induced retinopathy.
• Performed transcriptomic, metabolic, RNA pull-down, and mass spectrometry analyses.

Main Results:

• tsRNA-1599 expression is upregulated in ocular angiogenesis models.
• Silencing tsRNA-1599 inhibits endothelial cell proliferation, migration, and angiogenesis in vitro and in vivo.
• tsRNA-1599 reduces glycolysis and NAD+/NADH production by regulating HK2 expression via YBX1 interaction, independent of VEGF signaling.

Conclusions:

• tsRNA-1599 promotes ocular angiogenesis by reprogramming endothelial cell glycolysis.
• Targeting tsRNA-1599 represents a potential therapeutic strategy for ocular neovascular diseases.