Serine supplementation suppresses hypoxia-induced pathological retinal angiogenesis

Area of Science:

• Ophthalmology
• Metabolic pathways
• Cellular metabolism

Background:

• Pathological retinal neovascularization is a major cause of vision loss.
• This process is linked to hypoxia, dysmetabolism, and energy deficiency in retinal neurons.
• Altered serine metabolism is implicated in neovascularization associated with certain eye conditions.

Purpose of the Study:

• To investigate the role of serine metabolism in suppressing hypoxia-driven retinal neovascularization.
• To explore serine supplementation as a potential therapeutic strategy for neovascular eye diseases.
• To elucidate the underlying mechanisms of serine's protective effects in a mouse model.

Main Methods:

• Utilized the oxygen-induced retinopathy (OIR) mouse model.
• Administered systemic serine or a serine/glycine-deficient diet to OIR pups.
• Conducted metabolomics, lipidomics, proteomics, and single-cell RNA sequencing on retinal tissues.
• Investigated the role of mitochondrial fatty acid oxidation (FAO) and oxidative phosphorylation (OXPHOS) using specific inhibitors.

Main Results:

• Systemic serine supplementation reduced retinal neovascularization; deficiency exacerbated it.
• Serine treatment enhanced mitochondrial fatty acid oxidation and oxidative phosphorylation.
• Increased phosphatidylcholine levels and altered gene expression related to mitochondrial respiration and angiogenesis were observed.
• High mobility group box 1 protein (HMGB1) was identified as a potential mediator.

Conclusions:

• Serine supplementation shows promise for treating neovascular eye diseases.
• The therapeutic effect is mediated by enhanced retinal mitochondrial metabolism and lipid utilization.
• Targeting serine metabolism may suppress key drivers of uncontrolled angiogenesis and prevent vision loss.