Chlorogenic acid attenuates diabetic retinopathy by reducing VEGF expression and inhibiting VEGF-mediated retinal neoangiogenesis
Xiyu Mei1, Lingyu Zhou1, Tianyu Zhang1
1The MOE Key Laboratory for Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Abstract:
Diabetic retinopathy (DR) is one of the most common and serious complications of diabetes mellitus (DM). This study aims to investigate the amelioration of chlorogenic acid (CGA) on proliferative DR (PDR) via focusing on inhibiting retinal neoangiogenesis. CGA reduced the increased cell proliferation, migration and tube formation induced by vascular endothelial growth factor (VEGF) in human retinal endothelial cells (HREC) and choroid-retinal endothelial RF/6A cells. CGA abrogated VEGF-induced the phosphorylation of VEGFR2 and its downstream mitogen-activated extracellular regulated kinase (MEK1/2), extracellular regulated protein kinase (ERK1/2) and p38 kinase. CGA reduced high glucose (HG)-induced the activation of microglia BV-2 cells. CGA also reduced HG-induced the increased VEGF expression and hypoxia-inducible factor 1-alpha (HIF-1α) translocation into nucleus in BV2 cells. Retinal immunofluorescence staining with cluster of differentiation 31 (CD31) and retinal histopathological observation both demonstrated that CGA (1, 10mg/kg) decreased the increased retinal vessels in streptozotocin (STZ)-induced hyperglycemic mice. CGA reduced the elevated serum VEGF level and microglia activation in STZ-induced hyperglycemic mice. In conclusion, CGA inhibits retinal neoangiogenesis during the process of DR by abrogating HG-induced HIF-1α-mediated paracrine VEGF expression in microglia cells and inhibiting VEGF-induced angiogenesis in retinal endothelial cells.
Insights
Chlorogenic acid (CGA) effectively inhibits diabetic retinopathy (DR) by reducing retinal blood vessel growth. It targets key pathways involved in inflammation and new blood vessel formation, offering a potential therapeutic strategy for DR.
Area of Science:
- Ophthalmology
- Endocrinology
- Pharmacology
Background:
- Diabetic retinopathy (DR) is a leading cause of vision loss in diabetes mellitus (DM).
- Proliferative DR (PDR) is characterized by abnormal retinal blood vessel growth (neoangiogenesis).
- Current treatments for DR have limitations, necessitating novel therapeutic approaches.
Purpose of the Study:
- To investigate the potential of chlorogenic acid (CGA) in ameliorating PDR.
- To elucidate the mechanisms by which CGA inhibits retinal neoangiogenesis.
- To assess CGA's effects on high glucose-induced cellular changes relevant to DR.
Main Methods:
- In vitro studies using human retinal endothelial cells (HREC) and RF/6A cells treated with vascular endothelial growth factor (VEGF).
- Assessment of signaling pathways including VEGFR2, MEK1/2, ERK1/2, and p38 kinase.
- In vitro studies using microglia BV-2 cells exposed to high glucose (HG).
- In vivo studies using streptozotocin (STZ)-induced hyperglycemic mice.
Main Results:
- CGA suppressed VEGF-induced proliferation, migration, and tube formation in endothelial cells.
- CGA inhibited VEGF-induced phosphorylation of VEGFR2 and downstream kinases.
- CGA reduced high glucose-induced microglia activation and VEGF expression.
- CGA decreased retinal neovascularization and serum VEGF levels in hyperglycemic mice.
Conclusions:
- CGA demonstrates anti-angiogenic properties relevant to PDR.
- CGA mitigates high glucose-induced inflammation and VEGF production in microglia.
- CGA inhibits retinal neoangiogenesis by targeting both endothelial cells and microglia-mediated pathways.
