A diabetes-induced change of MDM2 SNP309T→G contributes to aberrant retinal angiogenesis - PubMed
6 hours ago
- #MDM2 SNP309G
- #diabetic retinopathy
- #angiogenesis
- MDM2 SNP309G is associated with proliferative diabetic retinopathy (PDR) and contributes to pathological angiogenesis.
- 60.1% of individuals with PDR harbored MDM2 SNP309G in fibrovascular membranes (FVMs), with 20.9% showing a T→G substitution at position 309.
- Vitreous humor from PDR patients had significantly higher levels of the oxidative DNA damage biomarker 8-oxo-2'-deoxyguanosine compared to controls.
- Chronic high glucose exposure in retinal endothelial cells promoted MDM2 SNP309T to G conversion and increased MDM2 protein levels.
- Prime editing to introduce MDM2 SNP309G enhanced high-glucose-induced angiogenic responses in vitro.
- Mice with MDM2 SNP309G exhibited increased retinal levels of MDM2, HIF-1α, phosphorylated VEGFR2, and VEGF, leading to exacerbated pathological angiogenesis.
- Targeting the second promoter of MDM2 may offer a novel therapeutic strategy for preventing aberrant angiogenesis in PDR.