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Published on: April 3, 2016
Quercetin ameliorates SIRT1-mediated oxidative stress and inflammation to attenuate ciliary muscle remodeling in
Yuanting Yang1, Miao Zhang1, Ruixue Zhang1
1Shandong University of Traditional Chinese Medicine, Jinan 250002, China.
Abstract:
This study aimed to investigate the role of quercetin in myopic ciliary muscle remodeling through the regulation of SIRT1 expression. To this end, a randomized controlled trial was conducted using negative lens-induced myopic (LIM) guinea pig models for durations of 4 weeks and 6 weeks, with subjects administered quercetin (QUE) or SRT1720. Changes in axial lengths and refractive errors were measured at 4 and 6 weeks. Subsequently, protein expression (e.g., SIRT1, KEAP1, NRF2, MMP-2, and TIMP-2) in ciliary muscles was analyzed by Western blotting, while the expression of inflammatory cytokines (e.g., TNF-α, IL-6, and IL-10) was quantified via ELISA, and ciliary muscle morphologies were assessed using hematoxylin and eosin (H&E) staining and optical coherence tomography (OCT). Calcium fluxes, reactive oxygen species (ROS) levels, and mitochondrial membrane potentials (ΔΨm) were measured via noninvasive microtests and flow cytometry. Compared with the LIM group, the QUE and SIRT1 activator (SRT1720) intervention groups presented significantly reduced axial elongation amounts and refractive errors (P < 0.01), along with thickened ciliary muscles and improved fiber alignments. Additionally, the calcium influx and ROS levels were significantly reduced, and the ΔΨm levels were partially restored. Furthermore, Western blotting revealed upregulated SIRT1, NRF2, and TIMP-2 expression but downregulated KEAP1 and MMP-2 expression in the intervention groups, and ELISA revealed decreased inflammatory responses. In conclusion,quercetin could play a protective role by increasing the expression of SIRT1, which in turn alleviated KEAP1/NRF2-induced oxidative stress and mitigated NF-κB-driven inflammatory damage, thereby ameliorating ciliary muscle remodeling and potentially delaying the progression of myopia.
Insights
Quercetin may protect against myopia by increasing SIRT1 expression, reducing oxidative stress and inflammation in ciliary muscles. This natural compound shows potential in delaying myopia progression in animal models.
Area of Science:
- Ophthalmology
- Molecular Biology
- Pharmacology
Background:
- Myopic ciliary muscle remodeling is a key factor in myopia progression.
- Oxidative stress and inflammation contribute to ciliary muscle dysfunction in myopia.
- SIRT1 (Sirtuin 1) is implicated in cellular protection and metabolic regulation.
Purpose of the Study:
- To investigate the protective role of quercetin (QUE) in myopic ciliary muscle remodeling.
- To explore the mechanism involving SIRT1 expression and its downstream effects.
- To evaluate quercetin's impact on oxidative stress, inflammation, and ciliary muscle morphology.
Main Methods:
- Randomized controlled trial using negative lens-induced myopic (LIM) guinea pig models.
- Administration of quercetin (QUE) or SIRT1 activator (SRT1720).
- Assessment of axial length, refractive error, ciliary muscle morphology (H&E, OCT), protein expression (Western blotting), cytokine levels (ELISA), calcium flux, ROS, and mitochondrial membrane potential (flow cytometry).
Main Results:
- Quercetin and SRT1720 significantly reduced axial elongation and refractive errors.
- Improved ciliary muscle thickness and fiber alignment observed in intervention groups.
- Reduced calcium influx and ROS levels, with partial restoration of mitochondrial membrane potential.
- Upregulation of SIRT1, NRF2, and TIMP-2; downregulation of KEAP1 and MMP-2.
- Decreased inflammatory cytokine levels (TNF-α, IL-6) and NF-κB pathway activation.
Conclusions:
- Quercetin ameliorates ciliary muscle remodeling and delays myopia progression in a guinea pig model.
- The protective effect is mediated by increased SIRT1 expression, alleviating oxidative stress (KEAP1/NRF2 pathway) and inflammation (NF-κB pathway).
- Quercetin demonstrates potential as a therapeutic agent for myopia control.

