Work

Quercetin-loaded exosomes delivery system prevents myopia progression by targeting endoplasmic reticulum stress and ferroptosis in scleral fibroblasts

Year: 2025

Type: article

Abstract: Myopia, a predominant cause of visual impairment, is often associated with scleral extracellular matrix (ECM) remodeling and axial elongation. Currently, effective therapeutic strategies for addressing scleral ECM remodeling remain limited, necessitating the development of new treatments. Quercetin, a natural flavonoid, has been shown to alleviate ECM remodeling. However, its hydrophobic nature limits clinical application. To address this, we developed a quercetin-loaded exosome delivery system (Exo-Que) to enhance quercetin bioavailability and investigated its effects and mechanisms in myopia prevention. This system exhibited excellent aqueous solubility, enhanced corneal permeability, and prolonged precorneal retention, enabling low-dose administration with significant efficacy. In the initial phase of treatment, Exo-Que showed a pronounced myopia prevention effect, with reductions of 58.41% in refractive error progression and 38.46% in axial length growth after two weeks of treatment. As the treatment duration extended to four weeks, its therapeutic efficacy remained robust, achieving reductions of 59.97% and 35.85%, respectively. The therapeutic efficacy of Exo-Que was comparable to that of the 0.1% atropine group (at two weeks, reducing 59.07% and 35.9%, respectively; at four weeks, 59.84% and 37.74%, respectively). Mechanistically, Exo-Que inhibited the activation of the IRE1-XBP1, PERK-eIF2, and ATF6 pathways, alleviating endoplasmic reticulum stress. Furthermore, it suppressed ferroptosis by modulating GRP78-ACSL4 and GRP78-GPX4 protein interactions, thus mitigating ECM remodeling and slowing myopia progression. Besides, Exo-Que showed excellent biosafety in both in vitro and in vivo studies. Collectively, these results highlight the promising therapeutic potential of Exo-Que for myopia prevention.

Source: Materials Today Bio

DOI: 10.1016/j.mtbio.2025.101896

Authors: Lianghui Zhao, Xiaoyun Dong, Bin Guo, Jike Song, Hongsheng Bi

Institutions: Shandong University of Traditional Chinese Medicine, Shandong Shierming Eye Hospital, Shandong Academy of Chinese Medicine

Language: English

Topic: Ophthalmology and Visual Impairment Studies

Subfield: Epidemiology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,400