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Published on: December 9, 2022
Rosmarinic acid suppresses retinal neovascularization via cell cycle arrest with increase of p21(WAF1) expression
Jeong Hun Kim1, Byung Joo Lee, Jin Hyoung Kim
1Department of Ophthalmology, College of Medicine, Seoul National University & Seoul Artificial Eye Center Clinical Research Institute, Seoul National University Hospital, Seoul 110-744, Republic of Korea.
Insights
Rosmarinic acid inhibits retinal neovascularization by causing cell cycle arrest in endothelial cells. This natural compound shows promise for treating retinopathy of prematurity and other sight-threatening conditions.
Area of Science:
- Ophthalmology
- Cell Biology
- Pharmacology
Background:
- Pathological angiogenesis causes blindness in conditions like retinopathy of prematurity (ROP).
- ROP is a leading cause of childhood blindness, despite current therapies.
- Effective treatments targeting retinal neovascularization are crucial.
Purpose of the Study:
- To investigate the anti-angiogenic potential of rosmarinic acid.
- To determine the mechanism of rosmarinic acid's effect on retinal endothelial cells.
- To evaluate rosmarinic acid's efficacy and safety in a mouse model of ROP.
Main Methods:
- Assessed rosmarinic acid's effect on retinal endothelial cell proliferation and in vitro tube formation.
- Analyzed cell cycle distribution (G0/G1, S, G2/M phases) and p21(WAF1) expression.
- Utilized a mouse model of retinopathy of prematurity to assess in vivo efficacy and retinal toxicity.
Main Results:
- Rosmarinic acid dose-dependently inhibited retinal endothelial cell proliferation and in vitro angiogenesis.
- It induced G2/M phase cell cycle arrest and increased p21(WAF1) expression.
- Rosmarinic acid significantly suppressed retinal neovascularization in vivo without causing toxicity.
Conclusions:
- Rosmarinic acid exhibits potent anti-angiogenic activity against retinal neovascularization.
- Its mechanism involves inducing cell cycle arrest and upregulating p21(WAF1).
- Rosmarinic acid is a potential therapeutic agent for retinopathy of prematurity and other vasoproliferative retinopathies.
Abstract:
Pathological angiogenesis is the most common cause of blindness at all ages including retinopathy of prematurity, diabetic retinopathy, and age-related macular degeneration. Despite advances in therapy, retinopathy of prematurity remains the most sight-threatening vaso-proliferative retinopathy in children. Herein, we demonstrated that rosmarinic acid has an anti-angiogenic activity to retinal neovascularization in a mouse model of retinopathy of prematurity, which is related to cell cycle arrest with increase of p21(WAF1). Rosmarinic acid significantly inhibited the proliferation of retinal endothelial cells in a dose-dependent manner, and inhibited in vitro angiogenesis of tube formation. Interestingly, the anti-proliferative activity of rosmarinic acid on retinal endothelial cells was related to G2/M phase cell cycle arrest in a dose-dependent manner. With treatment of rosmarinic acid, retinal endothelial cells in G2/M phase increased whereas those in G0/G1 and S phases decreased, which was accompanied by increase of p21(WAF1) expression in a dose-dependent manner. Moreover, rosmarinic acid effectively suppressed retinal neovascularization in a mouse model of retinopathy of prematurity, and showed no retinal toxicity. These data suggest rosmarinic acid could be a potent inhibitor of retinal neovascularization and may be applied in the treatment of other vasoproliferative retinopathies.
