A diabetes-induced change of MDM2 SNP309T→G contributes to aberrant retinal angiogenesis
Authors' conclusion
These findings suggest that MDM2 SNP309G drives a positive feedback loop involving MDM2 and VEGF signalling in vascular endothelial cells, thereby promoting pathological angiogenesis. Targeting the second promoter of MDM2 may represent a novel therapeutic strategy for preventing aberrant angiogenesis in PDR.
Study context
- Population
- Individuals with proliferative diabetic retinopathy (PDR) (blood and fibrovascular membranes), individuals with proliferative vitreoretinopathy (PVR) (epiretinal membranes, vitreous controls), primary HRECs and humanised C57BL/6J miceindividuals with PDR
- Participants
- 110 individuals
- Comparison
- MDM2 SNP309G vs MDM2 SNP309T
- PDRn = 110
- Outcome
- Association of MDM2 SNP309G with PDR and its contribution to pathological angiogenesis
Methodological detailshuman genetic association, in vitro prime editing in HRECs, humanised mouse oxygen-induced retinopathy model, Sanger DNA sequencing for MDM2 SNP309 status, ELISA for vitreous 8-oxo-2'-deoxyguanosine, Quantitative RT-PCR and western blot for MDM2-mediated signalling
- Human genetic association
- In vitro prime editing in HRECs
- Humanised mouse oxygen-induced retinopathy model
- Sanger DNA sequencing for MDM2 SNP309 status
- ELISA for vitreous 8-oxo-2'-deoxyguanosine
- Quantitative RT-PCR and western blot for MDM2-mediated signalling
Main finding
As reported in the abstract
MDM2 SNP309G in PDR fibrovascular membranes
| Group | Value | T→G substitution at position 309 in fibrovascular membranes (FVMs) vs matched blood |
|---|---|---|
| MDM2 SNP309G | 60.1% | 20.9% |
MDM2 SNP309G
Value60.1%
T→G substitution at position 309 in fibrovascular membranes (FVMs) vs matched blood20.9%
Further findings
| Outcome | Fold difference |
|---|---|
| Vitreous 8-oxo-2'-deoxyguanosine, PDR vs PVRSignificantly higher with PDR | 7.8±1.2-fold |
High-glucose vitreous exposure of HRECs
- Conversion of MDM2 SNP309T to G
- 36.1%
- Suppressed 8-oxoguanine DNA glycosylase expression
- Increased MDM2 protein levels
Prime editing-mediated SNP309T→G in HRECs
- Conversion rate
- 51.6%
- Further enhanced high-glucose-induced MDM2 expression and in vitro angiogenic responses
Retinal signalling and neovascularisation in oxygen-induced retinopathy (OIR) mice
- Increased retinal MDM2, HIF-1α, phosphorylated VEGFR2, phosphorylated Erk1/2 and phosphorylated Sp1 with SNP309G vs SNP309T
- Elevated vitreous vascular endothelial growth factor (VEGF) with SNP309G
- Exacerbated pathological retinal angiogenesis in OIR with SNP309G
Original publication
A diabetes-induced change of MDM2 SNP309T→G contributes to aberrant retinal angiogenesis. Diabetologia. Published 2 March 2026. doi:10.
Composed by AI from the published abstract and checked against it. How Briefs are made →