GDF11 protects against glucotoxicity-induced mice retinal microvascular endothelial cell dysfunction and diabetic
1Department of Endocrinology, Nanhai District People's Hospital of Foshan, Foping Road 40, Foshan, 528200, Guangdong Province, China; Department of Endocrinology, Wuhan Fourth Hospital, Puai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hanzheng Road 473, Wuhan, 430070, Hubei Province, China.
Abstract:
Growth differentiation factor 11 (GDF11) has been implicated in the regulation of embryonic development and age-related dysfunction, including the regulation of retinal progenitor cells. However, little is known about the functions of GDF11 in diabetic retinopathy. In this study, we demonstrated that GDF11 treatment improved diabetes-induced retinal cell death, capillary degeneration, pericyte loss, inflammation, and blood-retinal barrier breakdown in mice. Treatment of isolated mouse retinal microvascular endothelial cells with recombinant GDF11 in vitro attenuated glucotoxicity-induced retinal endothelial apoptosis and the inflammatory response. The protective mechanisms exerted are associated with TGF-β/Smad2, PI3k-Akt-FoxO1 activation，and NF-κB pathway inhibition. This study indicated that GDF11 is a novel therapeutic target for diabetic retinopathy.
Insights
Growth differentiation factor 11 (GDF11) shows therapeutic potential for diabetic retinopathy by protecting retinal cells and improving blood-retinal barrier function in mice. GDF11 treatment offers a novel strategy against diabetes-induced retinal damage.
Area of Science:
- Ophthalmology
- Endocrinology
- Cell Biology
Background:
- Diabetic retinopathy (DR) is a leading cause of vision loss.
- The role of Growth Differentiation Factor 11 (GDF11) in DR pathogenesis is largely unknown.
- GDF11 is involved in embryonic development and age-related processes.
Purpose of the Study:
- To investigate the therapeutic potential of GDF11 in a mouse model of diabetic retinopathy.
- To elucidate the protective mechanisms of GDF11 in retinal cells under diabetic conditions.
Main Methods:
- GDF11 treatment was administered to mice with diabetes-induced retinopathy.
- In vitro studies involved treating isolated mouse retinal microvascular endothelial cells with recombinant GDF11.
- Molecular pathways including TGF-β/Smad2, PI3k-Akt-FoxO1, and NF-κB were analyzed.
Main Results:
- GDF11 treatment ameliorated diabetes-induced retinal cell death, capillary degeneration, pericyte loss, and inflammation in mice.
- GDF11 attenuated glucotoxicity-induced apoptosis and inflammation in retinal endothelial cells in vitro.
- Protective effects were linked to TGF-β/Smad2 and PI3k-Akt-FoxO1 pathway activation and NF-κB inhibition.
Conclusions:
- GDF11 demonstrates significant protective effects against diabetic retinopathy.
- GDF11 represents a promising novel therapeutic target for managing diabetic retinopathy.
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