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Updated: Jun 3, 2025
Retinal Explant of the Adult Mouse Retina as an Ex Vivo Model for Studying Retinal Neurovascular Diseases
Published on: December 9, 2022
SREBF1 facilitates pathological retinal neovascularization by reprogramming the fatty acid metabolism of endothelial
Hangjia Zuo1, Xianyang Liu2, Yakun Wang1
1The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Prevention and Treatment on Major Blinding Diseases, Chongqing Eye Institute, Chongqing Branch (Municipality Division) of National Clinical Research Center for Ocular Diseases, Chongqing, 400016, PR China; Chongqing Medical University, Chongqing, PR China.
Insights
Sterol Regulatory Element-Binding Protein 1 (SREBF1) drives pathological neovascularization in retinopathy of prematurity (ROP) by altering lipid metabolism. Targeting SREBF1 shows promise for treating this vision-threatening infant disease.
Area of Science:
- Ophthalmology
- Molecular Biology
- Developmental Biology
Background:
- Retinopathy of prematurity (ROP) is a leading cause of vision loss in premature infants.
- The molecular mechanisms driving ROP pathogenesis are not fully understood.
- Identifying novel therapeutic targets for ROP is crucial.
Purpose of the Study:
- To investigate the role of Sterol Regulatory Element-Binding Protein 1 (SREBF1) in the pathogenesis of retinopathy of prematurity (ROP).
- To explore the molecular mechanisms by which SREBF1 influences retinal neovascularization.
- To assess the therapeutic potential of targeting SREBF1 in ROP.
Main Methods:
- Utilized the oxygen-induced retinopathy (OIR) mouse model.
- Performed endothelial functional assays, Western blotting, RT-qPCR, and immunofluorescence staining.
- Employed Co-Immunoprecipitation (Co-IP) to analyze molecular interactions.
Main Results:
- SREBF1 expression was significantly elevated in the OIR mouse model and hypoxic human retinal microvascular endothelial cells (HRMECs).
- In vivo and in vitro interventions targeting SREBF1 reduced pathological neovascularization.
- SREBF1 modulates lipid metabolism in HRMECs by regulating ACC1 and FASN, impacting proliferation, migration, and tube formation via the HIF-1α/TGF-β pathway.
Conclusions:
- SREBF1 plays a critical role in promoting pathological retinal neovascularization in ROP.
- SREBF1's mechanism involves reprogramming HRMECs through lipid metabolism and the HIF-1α/TGF-β signaling pathway.
- SREBF1 represents a potential therapeutic target for retinopathy of prematurity.
Abstract:
Retinopathy of prematurity (ROP) is a proliferative retinal vascular disorder that critically affects the visual development of premature infants, potentially leading to irreversible vision loss or even blindness. Despite its significance, the underlying mechanisms of this disease remain insufficiently understood. In this study, we utilized the oxygen-induced retinopathy (OIR) mouse model and conducted endothelial functional assays to explore the role of Sterol Regulatory Element-Binding Protein 1 (SREBF1) in ROP pathogenesis. SREBF1 expression levels, along with its downstream targets, were investigated through Western blotting, RT-qPCR, and immunofluorescence staining techniques. Furthermore, Co-Immunoprecipitation (Co-IP) was employed to examine the molecular mechanisms involved. Our results demonstrated a significant increase in SREBF1 expression in both the OIR mouse model and hypoxic primary human retinal microvascular endothelial cells (HRMECs). Interventions conducted both in vivo and in vitro showed notable efficacy in reducing pathological neovascularization. Importantly, we discovered that SREBF1 plays a key role in modulating lipid metabolism in HRMECs by regulating the expression of ACC1 and FASN, leading to cellular reprogramming. This reprogramming influences HRMEC proliferation, migration, and tube formation through the HIF-1α/TGF-β signaling pathway, ultimately contributing to pathological retinal neovascularization. These findings provide new insights into the role of SREBF1 in angiogenesis within the context of ROP, offering potential therapeutic targets for the management and treatment of this disease.
