Senescent endothelial cells: a potential target for diabetic retinopathy
Ying-Lu Liao1,2, Yi-Fan Fang1, Jia-Xing Sun1
1Department of Ophthalmology, Eye Institute of Chinese PLA, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
Abstract:
Diabetic retinopathy (DR) is a diabetic complication that results in visual impairment and relevant retinal diseases. Current therapeutic strategies on DR primarily focus on antiangiogenic therapies, which particularly target vascular endothelial growth factor and its related signaling transduction. However, these therapies still have limitations due to the intricate pathogenesis of DR. Emerging studies have shown that premature senescence of endothelial cells (ECs) in a hyperglycemic environment is involved in the disease process of DR and plays multiple roles at different stages. Moreover, these surprising discoveries have driven the development of senotherapeutics and strategies targeting senescent endothelial cells (SECs), which present challenging but promising prospects in DR treatment. In this review, we focus on the inducers and mechanisms of EC senescence in the pathogenesis of DR and summarize the current research advances in the development of senotherapeutics and strategies that target SECs for DR treatment. Herein, we highlight the role played by key factors at different stages of EC senescence, which will be critical for facilitating the development of future innovative treatment strategies that target the different stages of senescence in DR.
Insights
Diabetic retinopathy (DR) involves endothelial cell (EC) senescence. Targeting senescent ECs offers promising new senotherapeutics for DR treatment, addressing limitations of current therapies.
Area of Science:
- Ophthalmology
- Endocrinology
- Cell Biology
Background:
- Diabetic retinopathy (DR) is a significant complication of diabetes, leading to vision loss.
- Current treatments for DR, mainly antiangiogenic therapies targeting vascular endothelial growth factor, have limitations due to DR's complex pathogenesis.
- Emerging evidence implicates premature endothelial cell (EC) senescence in hyperglycemia as a key factor in DR development.
Purpose of the Study:
- To review the inducers and mechanisms of EC senescence in diabetic retinopathy pathogenesis.
- To summarize current research on senotherapeutics and strategies targeting senescent ECs (SECs) for DR treatment.
- To highlight key factors in EC senescence stages for developing innovative DR treatments.
Main Methods:
- Literature review focusing on endothelial cell senescence in diabetic retinopathy.
- Analysis of emerging studies on senotherapeutics and targeting senescent endothelial cells.
- Identification of key factors involved in different stages of endothelial cell senescence.
Main Results:
- Premature EC senescence in hyperglycemia plays multifaceted roles in DR pathogenesis.
- Targeting SECs presents a promising therapeutic avenue for DR, complementing existing strategies.
- Understanding EC senescence mechanisms is crucial for advancing DR treatment.
Conclusions:
- Senotherapeutics targeting SECs represent a novel and promising approach for diabetic retinopathy.
- Further research into the specific roles of EC senescence at different disease stages is critical.
- Innovative strategies targeting EC senescence could overcome limitations of current antiangiogenic therapies for DR.
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