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Endothelial RAB5IF is required for pathological and developmental retinal angiogenesis
Wen Bai1, De-Pei Yin2, Gang Chen3
1The Affiliated Eye Hospital, Nanjing Medical University, Nanjing, China.
Nature Communications
|December 13, 2025
Summary
Mitochondrial protein RAB5 interacting factor (RAB5IF) is crucial for retinal angiogenesis. It regulates SUMO2 protein levels, which are essential for blood vessel development and preventing eye diseases.
Area of Science:
- Ophthalmology
- Molecular Biology
- Cell Biology
Background:
- Retinal angiogenesis is vital for vision but also implicated in diseases.
- Mitochondrial proteins' roles in this process are not fully understood.
Purpose of the Study:
- Investigate the role of mitochondrial protein RAB5IF in retinal angiogenesis.
- Elucidate the molecular mechanisms linking RAB5IF to vascular development and disease.
Main Methods:
- Utilized neonatal and adult mouse models (oxygen-induced retinopathy, laser-induced choroidal neovascularization).
- Employed proteomic sequencing and gene silencing techniques.
- Analyzed mitochondrial respiration, ribosome biogenesis, and protein SUMOylation.
Main Results:
- RAB5IF is a critical regulator of both physiological and pathological retinal angiogenesis.
- RAB5IF silencing impairs mitochondrial function and suppresses SUMO2 translation.
- SUMO2-mediated SUMOylation of Gαi1/3 is essential for VEGF signaling and pro-angiogenic activity.
Conclusions:
- A novel RAB5IF-SUMO2-Gαi1/3 signaling axis is identified as essential for retinal angiogenesis.
- This pathway presents potential therapeutic targets for neovascular eye diseases.
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