Sphingosine-1-Phosphate-derived 2-Hexadecenal is a central mediator of ocular neovascularization by inhibiting Sphingosine-1-Phosphate receptor 5 - PubMed
5 hours ago
- #ferroptosis
- #ocular_neovascularization
- #diabetic_retinopathy
- Sphingosine-1-phosphate (S1P) is a key mediator in vasculature and neovascular eye diseases, influencing angiogenesis, inflammation, and fibrosis.
- The reactive lipid aldehyde 2-hexadecenal (2-HD), a major metabolite of S1P, plays a central role in ocular neovascularization by inhibiting S1P receptor 5 (S1PR5).
- Loss of ALDH3B1 impairs 2-HD detoxification, leading to retinal vascular abnormalities in zebrafish, without affecting trunk vasculature.
- 2-HD accumulation disrupts iron homeostasis and induces ferroptosis through direct interaction with S1PR5, as shown by multi-omics analyses.
- Single-cell and RNA sequencing from human neovascular retinal samples identify S1PR5 as a clinically relevant target for treating conditions like diabetic retinopathy.