Glucose metabolism is one of the most important factors controlling endothelial cell (EC) proliferation, migration, and neovascularization 
. Blood-derived glucose penetrates the RPE and the blood–retinal barrier and arrives at the retina facilitated by sodium-independent glucose transporter 1 (Glut1) generating ATP by aerobic glycolysis 
. ECs rely on glycolysis rather than OXPHOS for ATP production and vessel sprouting, and ECs nearly double their glycolytic flux, particularly in tip cells exposed to angiogenic stimuli, such as VEGF 
. Glycolysis in ECs is modulated by the rate-limiting enzyme, 6-phosphofructo-2-kinase/fructose-2,6-biophosphatase 3 (PFKFB3). Pharmacological inhibition of PFKFB3 or EC-specific genetic deletion of Pfkfb3
inhibits pathological retinal neovascularization in mouse OIR 
. Promotion of glucose uptake during hyperoxia in rat OIR through the inhibition of mitochondrial uncoupling protein 2 (UCP2), a cellular glucose regulator that decreases glucose uptake through Glut1, attenuates the retinal vaso-obliteration and subsequent neovascularization 
. The adenosine A2a receptor (ADORA2A) promotes HIF-1-dependent endothelial cell glycolysis, and the EC-specific Adora2a
deletion decreases retinal neovascularization in mouse OIR 
. In addition, under physiological conditions, glycolysis converts glucose to energy, with less than 3% of glucose diverted into the polyol pathway, which reduces glucose to sorbitol and increases oxidative stress through the production of highly toxic advanced glycation end products 
. Aldose reductase is the rate-limiting enzyme in the polyol pathway, and the deletion of the enzyme reduces retinal neovascularization through the attenuation of oxidative stress and protects retinal neurons in mouse OIR 
. These findings suggest that targeting retinal glucose metabolism is an effective way to control pathological retinal angiogenesis.
Recently, single-cell RNA sequencing reveals that glycolysis gene expression is upregulated in proliferating ECs, but less in tip and immature ECs in a mouse model of choroidal neovascularization 
. Proliferating ECs also upregulated genes involved in one-carbon metabolism, nucleotide synthesis, TCA cycle and OXPHOS 
, suggesting the involvement of other metabolic pathways in modulating pathological ocular angiogenesis. Further exploration of their role in ROP is needed.